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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
- 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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