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LIPIDS OF PHYSIOLOGICAL SIGNIFICANCE & ITS ROLE IN HEALTH AND DISEASES Presented by, Shruti Sharma (D.Phil Scholar)
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Page 1: Presentationonlipid 100907041325-phpapp01

LIPIDS OF PHYSIOLOGICAL SIGNIFICANCE

amp

ITS ROLE IN HEALTH AND DISEASES

Presented by

Shruti Sharma

(DPhil Scholar)

Why lipids are important-Why lipids are important-

Lipids are important to the body because-

1) Important constituent of the cell membranes

2) Helps in the absorption of fat soluble vitamins

3) Maintains membrane fluidity

4) Acts as a thermal insulator and cellular metabolic regulator

5) Hormone synthesis

6) Organ padding

bull

Major lipids of physiological significance-Major lipids of physiological significance-

Fatty acids Fatty acids -- basic units of fat composed of chains of basic units of fat composed of chains of carbon atoms with an acid group at one end and hydrogen carbon atoms with an acid group at one end and hydrogen atoms attached all along their lengthatoms attached all along their length

Present as either esterified or unesterified form in fats and oilsPresent as either esterified or unesterified form in fats and oils

Classification of fatty acids-Classification of fatty acids-

Fatty acids

Saturated FA Unsaturated FA

Saturated fatty acids-Saturated fatty acids-

bull bull

Saturated fatty contains no double bonds (having no points of Saturated fatty contains no double bonds (having no points of

unsaturationunsaturation)) Saturated fats- considered as harmful It increases totalSaturated fats- considered as harmful It increases total

cholesterol level and TGs levelcholesterol level and TGs level

Hypercholestrolemic SFAs are-Myristic acid amp Lauric acidHypercholestrolemic SFAs are-Myristic acid amp Lauric acid

Unsaturated fatty acids-Unsaturated fatty acids-

Unsaturated fatty acid a fatty acid with one or more points of unsaturation Unsaturated fats are found in foods from both plant and animal sources Unsaturated fatty acids are further divided into monounsaturated fatty acids and polyunsaturated fatty acids

Divisions of unsaturated fatty acids-Divisions of unsaturated fatty acids-

UnsaturatedFatty acids

MUFA PUFA Eicosanoids

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 2: Presentationonlipid 100907041325-phpapp01

Why lipids are important-Why lipids are important-

Lipids are important to the body because-

1) Important constituent of the cell membranes

2) Helps in the absorption of fat soluble vitamins

3) Maintains membrane fluidity

4) Acts as a thermal insulator and cellular metabolic regulator

5) Hormone synthesis

6) Organ padding

bull

Major lipids of physiological significance-Major lipids of physiological significance-

Fatty acids Fatty acids -- basic units of fat composed of chains of basic units of fat composed of chains of carbon atoms with an acid group at one end and hydrogen carbon atoms with an acid group at one end and hydrogen atoms attached all along their lengthatoms attached all along their length

Present as either esterified or unesterified form in fats and oilsPresent as either esterified or unesterified form in fats and oils

Classification of fatty acids-Classification of fatty acids-

Fatty acids

Saturated FA Unsaturated FA

Saturated fatty acids-Saturated fatty acids-

bull bull

Saturated fatty contains no double bonds (having no points of Saturated fatty contains no double bonds (having no points of

unsaturationunsaturation)) Saturated fats- considered as harmful It increases totalSaturated fats- considered as harmful It increases total

cholesterol level and TGs levelcholesterol level and TGs level

Hypercholestrolemic SFAs are-Myristic acid amp Lauric acidHypercholestrolemic SFAs are-Myristic acid amp Lauric acid

Unsaturated fatty acids-Unsaturated fatty acids-

Unsaturated fatty acid a fatty acid with one or more points of unsaturation Unsaturated fats are found in foods from both plant and animal sources Unsaturated fatty acids are further divided into monounsaturated fatty acids and polyunsaturated fatty acids

Divisions of unsaturated fatty acids-Divisions of unsaturated fatty acids-

UnsaturatedFatty acids

MUFA PUFA Eicosanoids

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 3: Presentationonlipid 100907041325-phpapp01

Major lipids of physiological significance-Major lipids of physiological significance-

Fatty acids Fatty acids -- basic units of fat composed of chains of basic units of fat composed of chains of carbon atoms with an acid group at one end and hydrogen carbon atoms with an acid group at one end and hydrogen atoms attached all along their lengthatoms attached all along their length

Present as either esterified or unesterified form in fats and oilsPresent as either esterified or unesterified form in fats and oils

Classification of fatty acids-Classification of fatty acids-

Fatty acids

Saturated FA Unsaturated FA

Saturated fatty acids-Saturated fatty acids-

bull bull

Saturated fatty contains no double bonds (having no points of Saturated fatty contains no double bonds (having no points of

unsaturationunsaturation)) Saturated fats- considered as harmful It increases totalSaturated fats- considered as harmful It increases total

cholesterol level and TGs levelcholesterol level and TGs level

Hypercholestrolemic SFAs are-Myristic acid amp Lauric acidHypercholestrolemic SFAs are-Myristic acid amp Lauric acid

Unsaturated fatty acids-Unsaturated fatty acids-

Unsaturated fatty acid a fatty acid with one or more points of unsaturation Unsaturated fats are found in foods from both plant and animal sources Unsaturated fatty acids are further divided into monounsaturated fatty acids and polyunsaturated fatty acids

Divisions of unsaturated fatty acids-Divisions of unsaturated fatty acids-

UnsaturatedFatty acids

MUFA PUFA Eicosanoids

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 4: Presentationonlipid 100907041325-phpapp01

Classification of fatty acids-Classification of fatty acids-

Fatty acids

Saturated FA Unsaturated FA

Saturated fatty acids-Saturated fatty acids-

bull bull

Saturated fatty contains no double bonds (having no points of Saturated fatty contains no double bonds (having no points of

unsaturationunsaturation)) Saturated fats- considered as harmful It increases totalSaturated fats- considered as harmful It increases total

cholesterol level and TGs levelcholesterol level and TGs level

Hypercholestrolemic SFAs are-Myristic acid amp Lauric acidHypercholestrolemic SFAs are-Myristic acid amp Lauric acid

Unsaturated fatty acids-Unsaturated fatty acids-

Unsaturated fatty acid a fatty acid with one or more points of unsaturation Unsaturated fats are found in foods from both plant and animal sources Unsaturated fatty acids are further divided into monounsaturated fatty acids and polyunsaturated fatty acids

Divisions of unsaturated fatty acids-Divisions of unsaturated fatty acids-

UnsaturatedFatty acids

MUFA PUFA Eicosanoids

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 5: Presentationonlipid 100907041325-phpapp01

Saturated fatty acids-Saturated fatty acids-

bull bull

Saturated fatty contains no double bonds (having no points of Saturated fatty contains no double bonds (having no points of

unsaturationunsaturation)) Saturated fats- considered as harmful It increases totalSaturated fats- considered as harmful It increases total

cholesterol level and TGs levelcholesterol level and TGs level

Hypercholestrolemic SFAs are-Myristic acid amp Lauric acidHypercholestrolemic SFAs are-Myristic acid amp Lauric acid

Unsaturated fatty acids-Unsaturated fatty acids-

Unsaturated fatty acid a fatty acid with one or more points of unsaturation Unsaturated fats are found in foods from both plant and animal sources Unsaturated fatty acids are further divided into monounsaturated fatty acids and polyunsaturated fatty acids

Divisions of unsaturated fatty acids-Divisions of unsaturated fatty acids-

UnsaturatedFatty acids

MUFA PUFA Eicosanoids

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 6: Presentationonlipid 100907041325-phpapp01

Unsaturated fatty acids-Unsaturated fatty acids-

Unsaturated fatty acid a fatty acid with one or more points of unsaturation Unsaturated fats are found in foods from both plant and animal sources Unsaturated fatty acids are further divided into monounsaturated fatty acids and polyunsaturated fatty acids

Divisions of unsaturated fatty acids-Divisions of unsaturated fatty acids-

UnsaturatedFatty acids

MUFA PUFA Eicosanoids

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 7: Presentationonlipid 100907041325-phpapp01

Divisions of unsaturated fatty acids-Divisions of unsaturated fatty acids-

UnsaturatedFatty acids

MUFA PUFA Eicosanoids

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 8: Presentationonlipid 100907041325-phpapp01

Monounsaturated fatty acidsMonounsaturated fatty acids-- Monounsaturated fatty acid Monounsaturated fatty acid a fatty acid containing a fatty acid containing

one point of unsaturation found mostly in vegetable oils one point of unsaturation found mostly in vegetable oils

such as olive canola and peanutsuch as olive canola and peanut

They are considered as They are considered as beneficialbeneficial for human health for human health

MUFAMUFA

Cis FA Trans FA

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 9: Presentationonlipid 100907041325-phpapp01

Cis- unsaturated fatty acids-Cis- unsaturated fatty acids- In In ciscis bonds bonds the two pieces of the carbon chain on either side the two pieces of the carbon chain on either side

of the double bond are either both ldquouprdquo or both ldquodownrdquo such of the double bond are either both ldquouprdquo or both ldquodownrdquo such that both are on the same side of the moleculethat both are on the same side of the molecule

Significance ndash Significance ndash Decreases total cholesterol and TGs levelDecreases total cholesterol and TGs level Increases HDL levelIncreases HDL level

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 10: Presentationonlipid 100907041325-phpapp01

Trans unsaturated fatty acids-Trans unsaturated fatty acids- Trans fatty acids are produced by hydrogenation processTrans fatty acids are produced by hydrogenation process Hydrogen atoms are on the opposite sides of the moleculeHydrogen atoms are on the opposite sides of the molecule Egcis-oleic acid trans-elaidic acidEgcis-oleic acid trans-elaidic acid

PHYSIOLOGICAL EFFECTS OF TRANS FATTY ACIDS

- SERUM LIPIDS-SYSTEMIC INFLAMMATION -ENDOTHELIAL-CELL FUNCTION

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 11: Presentationonlipid 100907041325-phpapp01

SERUM LIPIDSmdash

gtraises levels of low-density lipoprotein (LDL) cholesterol reduces levels of high-density lipoprotein (HDL) cholesterol

gtincreases the ratio of total cholesterol to HDL cholesterol a powerful predictor of the risk of CHD

gtincrease the blood levels of triglycerides of Lp(a) lipoprotein and reduce the particle size of LDL cholesterol further raise the risk of CHD gttrans fatty acids have markedly adverse effects on serum lipids

Physiological effects of trans fatty acids continuedhellip

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 12: Presentationonlipid 100907041325-phpapp01

Systemic inflammationmdash

inflammation an independent risk factor for atherosclerosis sudden death from cardiac causes diabetes and heart failurethe inflammatory effects of trans fats may account in part for their effects on cardiovascular health

For example the difference in C-reactive protein levels 21 percent vs 09 percent intake an increase in cardiovascular risk of approximately 30 percent

Physiological effects of trans fatty acids continuedhellip

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 13: Presentationonlipid 100907041325-phpapp01

ENDOTHELIAL-CELL FUNCTION--ENDOTHELIAL-CELL FUNCTION--

increased levels of several markers of endothelial dysfunction for eg-soluble intercellular adhesion molecule soluble vascular-cell adhesion molecule and E-selectin

Physiological effects of trans fatty acids continuedhellip

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 14: Presentationonlipid 100907041325-phpapp01

Polyunsaturated fatty acids-Polyunsaturated fatty acids-

Polyunsaturated fatty acids (sometimes abbreviated PUFA) are those fatty acids where unsaturation occur more than two points found in nuts and vegetable oils such as safflower sunflower and soybean and in fatty fish

They possess protective role on human healthconsidered as beneficial for consumpmtion

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 15: Presentationonlipid 100907041325-phpapp01

Increase esterification process of cholesterol amp prevents its Increase esterification process of cholesterol amp prevents its absorptionabsorption

By increasing the synthesis of eicosanoidsBy increasing the synthesis of eicosanoids Acts as an anti platelet aggregating factor so decreases the Acts as an anti platelet aggregating factor so decreases the

chances of clot formationchances of clot formation Decreases the synthesis of the precursor of VLDL AND TGsDecreases the synthesis of the precursor of VLDL AND TGs Increases clearance of LDL cholesterolIncreases clearance of LDL cholesterol

PUFA continued-

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 16: Presentationonlipid 100907041325-phpapp01

Omega-3-fatty acids-

Benefits-

gtLower PGE2s levelgtAnti-inflammatorygtLower triglyceride and cholesterol levelsgtBenefits vision and gtbrain functiongtDecrease Skin gtinflammationgtInhibit platelet adhesion gtIncrease insulin sensitivity

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 17: Presentationonlipid 100907041325-phpapp01

Omega-6 fatty acids-Omega-6 fatty acids-

Linoleic fatty acid

Arachidonic acid

Benefits-Platelet aggregation cardiovascular diseases and inflammationReduce the symptoms of eczema and psoriasisClear up different types of acne

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 18: Presentationonlipid 100907041325-phpapp01

Eicosanoids-Eicosanoids- These compounds are derived from long chain polyenoic fatty These compounds are derived from long chain polyenoic fatty

acids (20-carbon)acids (20-carbon) Examples of eicosanoidsExamples of eicosanoids-- ProstaglandinsProstaglandins ProstacyclinesProstacyclines ThromboxanesThromboxanes LeukotrienesLeukotrienes lipoxinslipoxins

They have roles inInflammationFeverRegulation of blood pressureBlood viscosityMale fertilityFemale conceptionMuscle cotractionBlood clottingTissue growthRegulation of sleepwake cycleBronchocostrictionAsthma

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 19: Presentationonlipid 100907041325-phpapp01

Triglycerides-Triglycerides-

StructureGlycerol + 3 fatty acids

FunctionsEnergy source--9 kcals per gramForm of stored energy in adipose tissueInsulation and protectionCarrier of fat-soluble vitaminsSensory properties in food

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 20: Presentationonlipid 100907041325-phpapp01

Phospholipids- Phospholipids- main lipid constituent of cell main lipid constituent of cell membranemembrane

StructureGlycerol + 2 fatty acids + phosphate groupalso considered as derivative of lsquophosphatidic acidrsquo

FunctionsMain lipid constituent of cell membranesLipid transport as part of lipoproteinsEmulsifiersCell signalling process phospholipids

Phoscholine phosinositol cardiolipin lysophospholipid plasmalogens sphingomy

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 21: Presentationonlipid 100907041325-phpapp01

SterolsSterols--Steroids are the compounds contains cyclic steroid nucleus namely cyclo pentanophenanthrene ring

Cholesterol-best known steroid because of its association with atherosclerosis and heart diseases Contains same steroid nucleusExclusively present in animals

Functions---Bile acidsndash Sex hormonesndash Adrenal hormonesndash Vitamin D--Cardiac glycosides

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 22: Presentationonlipid 100907041325-phpapp01

Glycolipids-Glycolipids- --widely distributed in the body--widely distributed in the body Fatty acids + sphingosine +carbohydrateFatty acids + sphingosine +carbohydrate Also ka glycosphingolipidsAlso ka glycosphingolipids Present in cell membrane and nervous tissuesPresent in cell membrane and nervous tissues It contributes to cell surface carbohydrateIt contributes to cell surface carbohydrate Other glycolipids are-Other glycolipids are- Cerebrosides- simplest form of glycolipidscontains ceramidesCerebrosides- simplest form of glycolipidscontains ceramides eg Galactosylcerebrosideseg Galactosylcerebrosides glucosylcerebrosidesglucosylcerebrosides Gangliosides ndash predominantly found in ganglionsComplex Gangliosides ndash predominantly found in ganglionsComplex

glycolipidsglycolipids

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 23: Presentationonlipid 100907041325-phpapp01

Lipoproteins-Lipoproteins-

Lipoproteins are th macromolecular complex of lipids and proteins

Transportation of lipids in the blood

Structure of lipoproteins-

Hydrophobic lipids (TG CE) in coreHydrophilic lipids (UC PL) on surface

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 24: Presentationonlipid 100907041325-phpapp01

Classes of lipoproteinsClasses of lipoproteins--

ChylomicronsChylomicronsVLDLVLDL

LDLLDL HDL

gt 30 nmgt 30 nm 9ndash15 nm9ndash15 nm20ndash22 nm20ndash22 nm

Dlt1006 gml D=1019-1063gml D=1063-121 gml

Doi H et al Circulation 2000102670-676 Colome C et al Atherosclerosis 2000149295-302 Cockerill GW et al Arterioscler Thromb Vasc Biol 1995151987-1994

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 25: Presentationonlipid 100907041325-phpapp01

ApolipoproteinsmdashApolipoproteinsmdash

Apo AI (liver small intestine)Apo AI (liver small intestine) Structural activator of lecithincholesterol acyltransferase Structural activator of lecithincholesterol acyltransferase

(LCAT)(LCAT) Apo AII (liver)Apo AII (liver)

Structural inhibitor of hepatic lipase component of ligand Structural inhibitor of hepatic lipase component of ligand for HDL bindingfor HDL binding

Apo A-IV (small intestine)Apo A-IV (small intestine) Activator of LCAT modulator of lipoprotein lipase (LPL)Activator of LCAT modulator of lipoprotein lipase (LPL)

Apo A-V (liver)Apo A-V (liver) Direct functional role is unknown regulates TG levelsDirect functional role is unknown regulates TG levels

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 26: Presentationonlipid 100907041325-phpapp01

Apoprotein continuedhellipApoprotein continuedhellip

Apo B-100 (liver)Apo B-100 (liver) Structural synthesis of VLDL ligand for LDL-receptorStructural synthesis of VLDL ligand for LDL-receptor

Apo B-48 (small intestine)Apo B-48 (small intestine) Structural synthesis of chylomicrons derived from apo B-Structural synthesis of chylomicrons derived from apo B-

100 mRNA following specific mRNA editing100 mRNA following specific mRNA editing Apo E (liver macrophages brain)Apo E (liver macrophages brain)

Ligand for apoE receptor mobilization of cellular Ligand for apoE receptor mobilization of cellular cholesterolcholesterol

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 27: Presentationonlipid 100907041325-phpapp01

Apoprotein continuedhellipApoprotein continuedhellip

Apo C-I (liver)Apo C-I (liver) Activator of LCAT inhibitor of hepatic TGRL Activator of LCAT inhibitor of hepatic TGRL

uptakeuptake Apo C-II (liver)Apo C-II (liver)

Activator of LPL inhibitor of hepatic TGRL Activator of LPL inhibitor of hepatic TGRL uptakeuptake

Apo C-III (liver)Apo C-III (liver) Inhibitor of LPL inhibitor of hepatic TGRL Inhibitor of LPL inhibitor of hepatic TGRL

uptakeuptake

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 28: Presentationonlipid 100907041325-phpapp01

ChylomicronsChylomicrons- TG rich- TG rich

Synthesized in intestine

Transports endogenous TGs

Hydrophobic CoreHydrophobic CoreTriglyceride (93) Triglyceride (93) Cholesteryl Esters Cholesteryl Esters (1)(1)

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 29: Presentationonlipid 100907041325-phpapp01

VLDL-VLDL- rich in CE and TGs- rich in CE and TGs-

Surface Surface Monolayer Monolayer Phospholipids Phospholipids (12)(12)Free Cholesterol Free Cholesterol (14)(14)Protein (4)Protein (4)

Hydrophobic CoreHydrophobic CoreTriglyceride Triglyceride (65) Cholesteryl (65) Cholesteryl Esters (8)Esters (8)

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 30: Presentationonlipid 100907041325-phpapp01

LDL-LDL- cholesterol rich cholesterol rich

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (15)(15)Protein (22)Protein (22)

Synthesized from VLDL in blood circulation

Transports cholesterol from liver and delivers to other tissues

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 31: Presentationonlipid 100907041325-phpapp01

High density lipoprotein-High density lipoprotein-

Surface Monolayer Surface Monolayer Phospholipids (25)Phospholipids (25)Free Cholesterol Free Cholesterol (7)(7)Protein (45)Protein (45)

Promotes re-esterification process of cholesterol

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 32: Presentationonlipid 100907041325-phpapp01

HDL SubpopulationsHDL Subpopulations

Rye et al Atherosclerosis 1999145227-238

Apolipoprotein CompositionApolipoprotein Composition

A-I HDLA-I HDL A-IA-II HDLA-IA-II HDL A-II HDLA-II HDL

Particle ShapeParticle Shape

DiscoidalDiscoidal

SphericalSpherical

Lipid CompositionLipid Composition

TG CE and PLTG CE and PL

Particle SizeParticle Size

HDLHDL2b2b HDLHDL2a2a HDLHDL3a3a HDLHDL3b3b HDLHDL3c3c

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 33: Presentationonlipid 100907041325-phpapp01

The Effects of Various Types of Fat on Blood Lipid Levels

bull Saturated Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol bull Polyunsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Decreases HDL-cholesterol bull Monounsaturated Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 34: Presentationonlipid 100907041325-phpapp01

Omega-3 Fat ndash Decreases total cholesterol ndash Decreases LDL-cholesterol ndash Increases HDL-cholesterol ndash Decreases serum triglycerides bull Trans Fat ndash Increases total cholesterol ndash Increases LDL-cholesterol

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 35: Presentationonlipid 100907041325-phpapp01

Role of lipids in health and diseasesRole of lipids in health and diseases ndash ndash omega-3 FAsomega-3 FAs

Docosahexanoic acid and brain development-It is becoming increasingly evident that long-chain PUFA from the (n-3) family appear to be neuroprotective and that long-chain PUFA from the (n-6family) may also have unique properties in affecting neurobiology

bullIt is found in very high concentrations in the cell membranes of the retina and cerebral cortexbullWhelan et al(2008) focused on docosahexaenoic acid (DHA)4 a PUFA that is preferentially deposited in brain phospholipids and has been linked to dementia Parkinson disease Alzheimer disease (AD)cognitive function mental stability suicide depression bipolar disorders impulsivity aggression etc (3ndash10) The content of DHA in the brain is 12ndash15 10- to 20-fold higher than any other (n-3) PUFA

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 36: Presentationonlipid 100907041325-phpapp01

Arachidonic acid and the brain--

One of the most important changes in this field is the link between arachidonic acid (AA) content and brain function The level of AA in the brain is comparable to that of DHA At 8ndash11 of the fatty acid phospholipids it is severalfold higherthan any other (n-6) PUFA (by comparison linoleic acid content is 1)

Connell et al(2007) demonstrated that dietary AA appears to influence plasticity and preserve hippocampal membrane fluidity and may provide some protection to oxidative stress via the activation of peroxisomal proliferatoractivatedreceptor-g (17) Furthermore it has been shown that AA as well as DHA activates syntaxin-3 a critical factor in the growth and regeneration of neurons

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 37: Presentationonlipid 100907041325-phpapp01

Prevention of cancer-Prevention of cancer-

Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast prostate and colon cancer cell lines cultured outside the body

Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary prostate and intestinal tumors

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 38: Presentationonlipid 100907041325-phpapp01

Lipids related disordersLipids related disorders-- lipid disorderslipid disorders

Common disorders

Hypercholetrolemia

Hypertriglyceridemia

Hyperlipoproteinemia

ketosis

CVD

Fatty liver

Obesity

cancer

Uncommon disorders

Metabolic disorders of cerebrosides

Lipidoses lipid storage diseases

Multiple sclerosis

Infant respiratory distress syndrome

Xanthomatosis

Retinitis pigmentosa

Phrynoderma Toad skin

Disorders of EFAs deficiency

Zwellwegerrsquos disease

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 39: Presentationonlipid 100907041325-phpapp01

ATHEROSCLEROSIS

As LDL particles penetrate the walls of the arteries they become oxidized-LDL and next are scavenged by the bodyrsquos white blood cells

bull These foam cells are then deposited into the

lining of the artery wall

bull This process known as atherosclerosis causes

plaque deposits to enlarge artery walls to lose

elasticity and the passage through the artery to narrow

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 40: Presentationonlipid 100907041325-phpapp01

Diagrammatic representation of the disease (atherosclerosis)-

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 41: Presentationonlipid 100907041325-phpapp01

Metabolic disorders of cerebrosidesMetabolic disorders of cerebrosides

diseasesdiseases Enzyme Enzyme deficiencydeficiency

Lipid Lipid accumulatingaccumulating

symptomssymptoms

Tay ndashsachs Tay ndashsachs diseasedisease

hexosaminihexosaminidasedase

gangliosidesgangliosides MentalretardationblindnessmuscuMentalretardationblindnessmuscular weaknesslar weakness

Fabryrsquos Fabryrsquos diseasedisease

A-A-galactosidasegalactosidase

galactosylceramidegalactosylceramide Skin rasheskidney failureSkin rasheskidney failure

Krabbersquos Krabbersquos diseasedisease

B-B-galactosidasgalactosidasee

galactosylceramidgalactosylceramidee

Mental retardationcomplete loss Mental retardationcomplete loss of myelin sheathof myelin sheath

Gaucherrsquos Gaucherrsquos diseasedisease

B-B-glucosidaseglucosidase

glucosylceramideglucosylceramide Enlarged liver and spleen eroison Enlarged liver and spleen eroison of long bones mental retardationof long bones mental retardation

Niemann-Niemann-pick diseasepick disease

sphingomyesphingomyelinaselinase

sphingomyelinsphingomyelin Enlarged liver and spleenEnlarged liver and spleen

Farberrsquos Farberrsquos diseasedisease

ceramidaseceramidase ceramideceramide Dermatitisskeletal Dermatitisskeletal deformationhoarsenessdeformationhoarseness

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 42: Presentationonlipid 100907041325-phpapp01

Lipoprotein disordersLipoprotein disorders- Hyperlipoproteinemias-- Hyperlipoproteinemias-

Hy Hy LipotypesLipotypes

Metabolic defectMetabolic defect Increased plasma Increased plasma lipid mostlipid most

Risk of athersclerosisRisk of athersclerosis

ll Deficiency of Deficiency of lipoproteinlipaselipoproteinlipase

chylomicronschylomicrons increaseincrease

llalla Deficiency of Deficiency of LDLreceptorsLDLreceptors

cholesterolcholesterol Very highVery high

llbllb Overproduction of Overproduction of apo-bapo-b

TGs and cholesterolTGs and cholesterol highhigh

llllll Abnormality in apo -eAbnormality in apo -e TGs and cholesterolTGs and cholesterol highhigh

lvlv Overproduction of Overproduction of TGsTGs

TGsTGs Maymay not increaseMaymay not increase

vv --do----do-- Chylomicron and Chylomicron and VLDLVLDL

--do----do--

Ref- Harperrsquos biochemistryRef- Harperrsquos biochemistry

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 43: Presentationonlipid 100907041325-phpapp01

Infant repiratory distress syndrome-

Caused due to the deficiency of the lung surfactant dipalmitoyl lecithin

It prevents collapsing of the alveoli and also decreases the surface tension

Deficiency is common in young infants

Xanthomatosis-

Deposition of yellow-orange colours lipids occurs in the liver spleen and flat bones

Usually related with severe hypercholesterolemia and hyperlipidemia

Phrynoderma or Toad skin-

Caused due to the deficiency of essential fatty acids

Horny eruptions occurs on posterior and lateral limbspoor wound healing

Multiple sclerosis-

It is a demyelinating condition loss of both phospholipids and sphingolipids occurs from white matter Neurodegeneration is common

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 44: Presentationonlipid 100907041325-phpapp01

Defects in the metabolism of essential fatty acids -

Cystic fibrosisAcrodermatitis enterohepaticaHepato renal syndrome Crohnrsquos diseaseCirrhosis Alcoholism Reyes syndrome etc

Zwellwegerrsquos disease-

Rare disorder

occurs due to the accumulation of long chain polyenoic fatty acids in the brain

Causes loss of functions and neural degeneration

Dicarboxylic aciduria-

It is characterized by the excretion of C6-C10 dicarboxylic acid due to the lack of mitochondrial acyl coA dehydrogenase enzyme

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 45: Presentationonlipid 100907041325-phpapp01

Common Atherogenic dyslipidemias)

1048707 polygenic inheritancendash dietary componentndash secondarily enhanced byinsulin resistance (seefurther why)1048707 prognosis of combinedhyperlipidemia is worsethan that ofhypercholesterolemia1048707 main featuresndash impaired clearance of TAGby LPL (1048707 insulin) fromchylomicrons rarr increasedTAG and increased deliveryof TAG for liverndash increased production ofVLDL by liver (1048707 insulin)from TAG FFA from adiposetissue (1048707 insulin) andglucose (1048707 insulin)ndash therefore increasedconversion of VLDL to LDLndash low HDL

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 46: Presentationonlipid 100907041325-phpapp01

Fatty liver-Fatty liver-

When lipids accumulates excessively in liver then it causes fatty liver

Dropletes of TGs are found in the entire hepatic cytoplasm

this causes impairment in liver function

Fatty liver may occur due to two main reason-

1) Increased synthesis of TGs

2) Impairment in lipoprotein synthesis

Fatty liver is associated with the fibrotic changes and cirrhosis

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 47: Presentationonlipid 100907041325-phpapp01

Tangier Disease

gtAutosomal codominant disorder due to mutations in both alleles of ABC1 gene bull Extremely marked reduction in HDL-C and apoA-I bull Markedly accelerated catabolism of apoA-I andgtapoA-II bull Cholesterol accumulation minus Enlarged orange tonsils minus Hepatosplenomegaly minus Peripheral neuropathy

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 48: Presentationonlipid 100907041325-phpapp01

References--

1) Connell E Darios F Broersen K Gatsby N Peak-Chew SY Rickman CDavletov B Mechanism of arachidonic acid action on syntaxin- Munc18 EMBO Rep 20078414ndash9

2) GrannerK and RobertK(2006)Harperrsquos illustrated biochemistry 27th editionTata McGraw Hills publication

3)SatyanarayanU (2006)Biochemistry3rd edition Books and Allied (P)Ltd

4) Whelan J(2008)(n-6) and (n-3) Polyunsaturated Fatty Acids and the Aging Brain Food for Thought Abstract J Nutr 138 2521ndash2522

  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49
Page 49: Presentationonlipid 100907041325-phpapp01
  • Slide 1
  • Why lipids are important-
  • Major lipids of physiological significance-
  • Classification of fatty acids-
  • Saturated fatty acids-
  • Unsaturated fatty acids-
  • Divisions of unsaturated fatty acids-
  • Monounsaturated fatty acids-
  • Cis- unsaturated fatty acids-
  • Trans unsaturated fatty acids-
  • Slide 11
  • Slide 12
  • ENDOTHELIAL-CELL FUNCTION--
  • Polyunsaturated fatty acids-
  • Slide 15
  • Slide 16
  • Omega-6 fatty acids-
  • Eicosanoids-
  • Triglycerides-
  • Phospholipids- main lipid constituent of cell membrane
  • Sterols-
  • Glycolipids-
  • Lipoproteins-
  • Classes of lipoproteins-
  • Slide 25
  • Slide 26
  • Apoprotein continuedhellip
  • Chylomicrons- TG rich
  • VLDL- rich in CE and TGs-
  • LDL- cholesterol rich
  • High density lipoprotein-
  • HDL Subpopulations
  • Slide 33
  • Slide 34
  • Role of lipids in health and diseases ndash omega-3 FAs
  • Arachidonic acid and the brain--
  • Prevention of cancer-
  • Lipids related disorders-
  • Slide 39
  • Slide 40
  • Metabolic disorders of cerebrosides
  • Lipoprotein disorders- Hyperlipoproteinemias-
  • Slide 43
  • Slide 44
  • Common Atherogenic dyslipidemias
  • Fatty liver-
  • Tangier Disease
  • Slide 48
  • Slide 49

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