CH10 Lipid Metabolism

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iochemistry for Health Science Lipid Metabolism

hatchawin PETCHLERT, Ph.D. 1

LIPID METABOLISMLIPID METABOLISM

Chatchawin PetchlertChatchawin Petchlert

Dept. of Biochemistry, Burapha UniversityDept. of Biochemistry, Burapha University Petchlert C. 2

Processing of dietary lipids in vertebratesProcessing of dietary lipids in vertebrates

Petchlert C. 3

Mobilization ofMobilization of

triacylglycerols stored intriacylglycerols stored in

adipose tissueadipose tissue

Petchlert C. 4

DigestionDigestionDietary lipidsDietary lipids

TGTG CLCL PLPL

Short /Short /

MediumMediumLongLong FreeFree EsterEster

Emulsification by bile saltsEmulsification by bile salts

22--MG +MG +

FAFACLCL FAFA LysolecithinLysolecithin

Pancreaticlipase

PancreaticCL lipase

PancreaticPancreatic

phospholipasephospholipase

MICELLESMICELLES

IntestinalIntestinal

lumenlumen


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Petchlert C. 5

AbsorptionAbsorption

MICELLESMICELLESShort /Short /

MediumMedium

TGTG

GlycerolGlycerol

+ FA+ FAResynthesisResynthesis

of TGof TGCLCL PLPL

Bile saltBile salt

reabsorbedreabsorbed

in ileumin ileum

+ Albumin+ Albumin PortalPortal

veinvein

++

ApoproteinsApoproteins

ChylomicronChylomicron

LactealLacteal

SubclavianSubclavian

veinvein

HepaticHepatic

arteryartery

LiverLiver

Intestinal epithelialIntestinal epithelial

Petchlert C. 6

Entry of glycerol intoEntry of glycerol into

the glycolytic pathwaythe glycolytic pathway

Petchlert C. 7 Petchlert C. 8

Fatty acid entry into mitochondria via theFatty acid entry into mitochondria via the

acyl~carnitine/carnitine transporter.acyl~carnitine/carnitine transporter.


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Stage of fatty acid oxidation.Stage of fatty acid oxidation.

Stage1: A long-chain fatty acid is oxidized toyield acetyl residues in the form of acetyl~CoA.

This process is called -oxidation.

Stage2: The acetyl groups are oxidized to CO2via the TCA cycle

Stage3: Electrons derived from the oxidationsof stage1 and 2 pass to O2 via the mitochondrialrespiratory chain, providing the energy for ATPsynthesis by oxidative phosphorylation.



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Oxidation of propionyl~CoAOxidation of propionyl~CoA

produced byproduced by oxidation ofoxidation ofoddodd--number fatty acidsnumber fatty acids


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Petchlert C. 17

Role ofRole of --oxidation in theoxidation in theconversion of storedconversion of stored

triacylglycerols to glucosetriacylglycerols to glucose

in germinating seeds.in germinating seeds.

Petchlert C. 18

Comparison of the enzymes ofComparison of the enzymes of oxidation in gram+ andoxidation in gram+ and

gramgram-- bacteriabacteria


Formation of ketoneFormation of ketone

bodies from acetyl~CoA.bodies from acetyl~CoA.


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Petchlert C. 21

Extrahepatic tissues useExtrahepatic tissues use

ketone bodies as fuels.ketone bodies as fuels.

Petchlert C. 22

Ketone bodies formationKetone bodies formation

and export from the liver.and export from the liver.


The acetylThe acetyl--CoA carboxylase reaction.CoA carboxylase reaction.


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The overall process ofThe overall process of

palmitate synthesis.palmitate synthesis.



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Beginning of the secondBeginning of the second

round of the fatty acidround of the fatty acidsynthesis cycle.synthesis cycle.


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Subcellular localization of lipid metabolismSubcellular localization of lipid metabolism


The pentose phosphate pathway.The pentose phosphate pathway.

Production of NADPH by photosynthesis.Production of NADPH by photosynthesis.


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Filaments of acetyl~CoAFilaments of acetyl~CoA

carboxylasecarboxylase


Action of plantAction of plant

desaturases.desaturases.


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Regulation ofRegulation of

triacylglyceroltriacylglycerol

synthesis by insulinsynthesis by insulin

Petchlert C. 51

Biosynthesis ofBiosynthesis of

sphingolipidssphingolipids

Petchlert C. 52

Biosynthesis of sphingolipidsBiosynthesis of sphingolipids


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Petchlert C. 65

Lipoproteins

LDL HDL

Chylomicron VLDL +

+

proteinprotein

LPLP

originorigin

oo FF 1122 22 11 ALBALB

prepre

Petchlert C. 66

Distribution of Apoproteins

ChylomicronChylomicron VLDLVLDL LDLLDL HDLHDL

ApoAApoA

ApoB

ApoCApoC

ApoEApoE

ApoB

ApoB

ApoCApoC

ApoAApoA

ApoB

ApoCApoC

ApoEApoEApoEApoE


Functions of Lipoproteins

Chylomicron and VLDL are TG carriers tomuscle or adipose tissues

TGs in chylomicron come from the diets butTGs in VLDL are synthesized in the liver by

FA or acetyl CoA LDL and HDL are CL carriers

LDL is synthesized from VLDL but HDLcomes from small intestine, liver and VLDL

LDL delivers CL to peripheral cells, while HDLreturns it to the liver for excretion


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Uptake ofcholesterol by

receptor-mediated

endocytosis.


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Petchlert C. 73

AtherosclerosisAtherosclerosis

Petchlert C. 74

HDLHDL

Free CLFree CL

LCATLCAT

Nascent HDLNascent HDL

or Discoidalor Discoidal

prepre----HDLHDL

HDLHDL33 or Matureor Mature

CECE--rich HDLrich HDLHDLHDL22

CECE

LCAT : lecithinLCAT : lecithin--cholesterol acyltransferasecholesterol acyltransferase

Petchlert C. 75

HDL and Reverse Cholesterol TransportHDL and Reverse Cholesterol Transport

(Brown MS. And Goldstein JL. Atherosclerosis Review 1988 : 85(Brown MS. And Goldstein JL. Atherosclerosis Review 1988 : 85--94)94)

HDLHDL

VLDLVLDL LDLLDL

BB

BB

LDLLDL

receptorreceptor

SRSR--BIBI

receptorreceptor

LiverLiver

Peripheral cellsPeripheral cells

CL PoolCL Pool

ABCA1 transporterABCA1 transporter

LDL receptorLDL receptor

(Mulcahy JV. And Owen JS. SCIENCE & MEDICINE March/April 2002 :(Mulcahy JV. And Owen JS. SCIENCE & MEDICINE March/April 2002 : 7676--85)85)

Lipid Transfer ProteinLipid Transfer Protein

Petchlert C. 76

Regulation of cholesterolRegulation of cholesterol

biosynthesis balancebiosynthesis balance

synthesis with dietary uptake.synthesis with dietary uptake.


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Petchlert C. 77

Inhibitors of HMGInhibitors of HMG--CoACoA

synthasesynthase

Petchlert C. 78

Petchlert C. 79

An overview ofAn overview of

isoprenoidisoprenoidbiosynthesis.biosynthesis.

CH10 Lipid Metabolism

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