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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)血浆脂蛋白的分类electrophoresismethod:
♁§5.2Classificationofplasmalipoproteins-LipoproteinCM(chylomicron)-Lip
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