LipidMetabolismDiscussβ-oxidationoffattyacids.Explaintheclassification,propertiesandfunctionsofplasmalipoproteins.LearningOutcome3ProteinsCarbohydratesFatsandlipidsAcetyl-CoA

RespiratoryChainAminoacidsMonosaccharideGlycerolFattyacidCitricacidcycle

CO22HADP+Pi

ATP

H2O

SubstancemetabolismSection1OverviewLipidsaresubstancesthatareinsolubleorimmiscibleinwater,butsolubleinorganicsolvents.1.1Concept

LipidsLipoids

Fats(Triglyceride)TostoreandsupplyenergyPhospholipids

Glycolipids

Cholesterol

CholesterolesterTobestructuralcomponentsofcellularmembraneTypesoflipids1.2Digestionofdietarylipids

Position:

Requirement:inthesmallintestinepancreaticlipase

bilesalt(emulsification)bileacidsbilesaltmicelleHydrophilicsurfaceHydrophobicsurfacebilesaltpancreaticlipasetriglycerideFAEmulsificationofbilesaltemulsification

digestiveenzyme

triglyceridedietarylipids2-monoglyceride+2FAphosphatideslysophosphatide+FAphospholipaseA2cholesterolesterCholesterolesterasecholesterol+FApancreaticlipaseMixedmicellecolipaseDigestedproductsoftriglycerideareassembledinintestinalmucosacellsintowater-solublechylomicrons.

chylomicronscanbetransportedintheblood.

1.3DigestedproductsoflipidsareassembledinintestinalmucosacellsSection2TriglyceridemetabolismFatmobilization：

Thetriglyceridesstoredintheadipocytesarehydrolyzedbylipases,toproducefreefattyacids(FFA)andglycerol,whicharereleasedtotheblood,thisprocessiscalledfatmobilization.§2.1mobilizationofstoredtriglyceridesinadiposetissueiscatalyzedbyhormonesensitivelipaseTheactivityoftheenzymeisakeyfactortocontrolthereleaseoffattyacidsfromadiposetissue.Twolipolytichormones:GlucoganandepinephrineAntilipolyticHormones:insulinHormone-sensitiveadiposetissuelipase1.Activationoffattyacides2.Transportofacyl-CoAintothemitochondria

3.β-oxidationoffattyacids4.Acetyl-CoAenterTCAcyclecytoplasmmitochondriaProcedure

Position

mitochondriamitochondria§2.2Fattyacidsareoxidizedtoacetyl-CoA,NADH,andFADH2byβ-OxidationStage1

Activationoffattyacids

Acyl-CoA

Synthetase,whichlocatesonthecytoplasm,catalyzestheactivationoflongchainfattyacids.FattyacidAcyl-CoAStage2

Transportofacyl-CoAintothemitochondria

Carrier:

carnitineKeyenzyme:carnitine-acyl

transferaseⅠCytosol

transpoteracyl-carnitineⅡacyl-CoAcarnitine

HSCoA

OutermitochondriamembraneInnermitochondriamembraneMatrix*Ⅰ

acyl-CoA

HSCoA

carnitineacyl-carnitine

Carnitine-acyl

transferaseⅠCarnitine-acyl

transferase

ⅡStage3

β-oxidationoffattyacidsFourstepsinoneroundstep1:

Dehydrogenatestep2:

Hydrationstep3:

Dehydrogenatestep4:

ThiolyticcleavageDehydrogenate

HydrationDehydrogenateThiolyticcleavageAcyl-CoA

3-L-Hydroxyacyl-CoA3-Ketoacyl-CoAAcyl-CoA+acetyl-CoATrans-⊿2-Enoyl-CoA

NAD+NADH+H+H2OFADFADH2TCAcycleCoA-SHβ-Oxidationproducesacetyl-CoA(2Cless)Stage4:TCAcycleTheproductoftheβ-oxidationisintheformofFADH2,NADH,acetyl-CoA,onlyafterTCAcycleandoxidativephosphorylation,canATPbeproduced.ThiolyticcleavageCoA-SHacyl-CoAsynthetasecarnitineATPCoASHAMPPPiH2ORespiratorychain

1.5ATPTCA

Summaryofβ-oxidationcytoplasm

mitochondrialmatrixfattyacidacyl-CoAacyl-CoADehydrogenateFADFADH2trans-⊿2-Enoyl-CoAHydrationH2O3-L-Hydroxyacyl-CoADehydrogenate

NAD+NADH+H+3-Ketoacyl-CoAAcyl-CoA+acetyl-CoAH2O

2.5ATPRespiratorychain

Ketonebodiesarewater-solublefuelsnormallyexportedbytheliverbutoverproducedduringfastingorinuntreateddiabetesmellitus,includingacetoacetate,β-hydroxybutyrate,andacetone.§2.3KetoneBodiesFormationandUtilizationLocation:hepaticmitochondriaMaterial:acetyl-CoAKeyenzyme:HMG-CoAsynthaseTheformationofketonebodiesCO2CoASH

CoASH

NAD+NADH+H+β-hydroxybutyratedehydrogenaseHMG-CoA*synthase

β-KetothiolaseHMG-CoAlyaseHepaticmitochondriaacetoacetateacetoneβ-hydroxybutyrateAcetoacetyl-CoAAcetyl-CoAAcetyl-CoAFormationofketonebodiesUtilizationofketonebodiesβ-hydroxybutyrate

NAD+NADH+H+acetoacetateacetoacetyl-CoA2acetyl-CoA

succinyl-CoA

succinateCoA-SHLocation:extrahepatictissuesNormalphysiologicalresponsestocarbohydrateshortagescausethelivertoincreasetheproductionofketonebodiesfromtheacetyl-CoAgeneratedfromfattyacidoxidation.Ketonebodiesreplaceglucoseasthemajorsourceofenergyformanytissuesespeciallythebrain,heartandmusclesduringtimesofprolongedstarvation.BiologicalSignificancePlace:liver,kidney,intestineglycerolglycerol3-phosphateglyceraldehyde

3-phosphateDihydroxyacetonephosphate§2.4glycerolmetabolism§2.5SynthesisoffattyacidLocation:

cytosolofliver,adiposetissue,

kidney,brainandbreast.Precursor:acetyl-CoAOthermaterials:ATP,NADPH,CO2

Themainsourceofacetyl-CoA:acetyl-CoA

glucose（mitochondria）cytoplasmaerobicoxidationCitrate-pyruvatecycleThemainsourceofNADPH:PentosephosphatepathwayCitrate-pyruvatecycle

Processofsynthesis:(1)CarboxylationofAcetylCoA(2)Repetitivestepscatalyzedbyfattyacidsynthase(1)CarboxylationofAcetylCoA

Malonyl-CoA

servesasthedonoroftwo-carbonunit.

Acetyl-CoA

Carboxylaseisthekeyenzymeofthefattyacidsynthesispathway.Fattyacidsynthesisfromacetyl-CoA&malonyl-CoAoccursbyaseriesofreactions.(2)RepetitivestepscatalyzedbyfattyacidsynthaseFourstepsinoneround:step1:

Synthesisstep2:

Reductionstep3:

Dehydrationstep4:

Reduction

CH3CH2CH2CH2CH2CH2(CH2CH2)4CH2COOH

Acetyl-CoA

Malonyl-CoA

Theoverallreactionofsynthesis:

acetyl-CoA

+7malonyl-CoA

+

14NADPH+H+

palmitinicacid+7CO2

+6H2O+8HSCoA

+14NADP+Section5PlasmalipoproteinConcept:Allthelipidscontainedinplasma,includingfat,phosphalipids,cholesterol,cholesterolesterandfattyacid.Bloodlipidexistandtransportintheformoflipoprotein.§5.1bloodlipidbloodlipid+apolipoproteinlipoproteina.Tocombineandtransportlipids.b.Toregulatelipoproteinmetabolism.c.Torecognizethelipoproteinreceptors.FunctionofapolipoproteinGeneralstructureofalipoprotein（一）血漿脂蛋白的分類electrophoresismethod:

?§5.2Classificationofplasmalipoproteins-LipoproteinCM(chylomicron)-Lip