Lipidmetabolism脂类代谢

10.Lipidmetabolism,HuangxiaoLinyiuniversity,Keynotes,StructuresandrolesoffattyacidsFattyacidbreakdownFattyacidsynthesisTriacylglycerols,10.1Structuresandrolesoffattyacids,Fattyacidshavealonghydrocarbonchainwithaterminalcarboxylicacidgroup.Mostfattyacidshaveanevennumberofcarbonatomsinanunbranchedchain.Saturatedfattyacidshavenodoublebondsbetweenthecarbonatoms,whereasmono-andpolyunsaturatedfattyacidshaveoneormoredoublebonds.,Fattyacidshavefourmajorbiologicalroles:1)Theyarecomponentsofmembranes(glycerophospholipidsandsphingolipids)2)Severalproteinsarecovalentlymodifiedbyfattyacids.3)Theyactasenergystores(triacylglycerols)andfuelmolecules.4)Fattyacidderivativesserveashormonesandintracellularsecondmessengers.,10.2Fattyacidbreakdown,OverviewActivationTransportintomitochondria-oxidationpathwayEnergyyieldKetonebodies,1.overview,Fattyacidbreakdownbringsabouttheoxidationoflong-chainfattyacids.ThefattyacidsarefirstconvertedtotheiracylcoenzymeAderivativesandthendegradedbythesuccessiveremovaloftwo-carbonunitsfromtheendofthefattyacidasacetylCoA.,Incytosol,AcylCoAsynthetase,2.Fattyacidactivation,RCOOH,+,CoASH,RCOSCoA,AcylCoAsynthetase,ATP,AMP+PPi,Mg2+,H2O,2Pi,thereactionisirreversible,fattyacid,acylCoA,3.Transportintomitochondria,longerchainacylCoAsdonotreadilycrosstheinnermitochondrialmembrane,andrequireaspecifictransportmechanism.,RCO-SCoA,CoA-SH,transferase,(CH3)3N+,-CH2CH-,CH2COOH,OH,carnitine,(CH3)3N+,CH2CH,CH2COOH,RCO-O,acylcarnitine,R-COSCoA,H-SCoA,carnitine,R-CO-carnitine,R-CO-carnitine,H-SCoA,carnitine,R-COSCoA,transferase,-oxidation,transferase,Innermitochondrialmembrane,4.-Oxidationpathway,Oxidation(byFAD)HydrationOxidation(byNAD+)Thiolysis,oxidation,acylCoAdehydrogenase,FAD,FADH2,hydration,OH,RCH2,CH2,COSCoA,3-hydroxyacylCoA,1.5ATP,respiratorychain,R-CH2-CH2C-SCoA,|,OH,RCH2,CH,CH2,COSCoA,oxidation,thiolysis,（1）（2）（3）（4）,3-ketoacylCoA,RCH2C,SCoA,O,CH2CO,CoA-SH,ketothiolase,2.5ATP,respiratorychain,roundreaction,Oxidationofodd-chainfattyacid,RacemaseB12,CH3-CH2-COCoA,PropionylCoA,HOOC-CH2-CH2-COCoA,SuccinylCoA,5.Energyyield(C16:0),PalmitoylCoA+7FAD+7NAD+7CoA-SH+7H2O8acetylCoA+7FADH2+7(NADH+H+),Summary,2.-oxidation:7FADH2:10.5(14)ATPsproduced,7(NADH+H+):17.5(21)ATPsproduced,3.Tricarboxylicacidcycleandoxidativephosphorylation8acetylCoA:80(96)ATPsproduced.,Total106(129)ATPsproduced,1.FrompalmitatetopalmitoylCoAconsumed2ATPs,6.Ketonebodies,Acetoacetate,D-3-hydroxybutytateandacetonearecalledketonebodies.Theyareproducedintheliverandprovideanalternativesupplyoffuelforthebrainunderstarvationconditionsorindiabetes.,Doyouthinkthattheyoungmantakes250gofbutterperdayfor3days?,Really!,Oh,soStupid!theremustbelotsofketonebodiesinhisurine,10.3Fattyacidsynthesis,OverviewTransportintothecytosolThepathway,1.Overview,Fattyacidsynthesisinvolvesthecondensationoftwo-carbonunits,intheformofacetylCoA,toformlonghydrocarbonchainsinaseriesofreactions.,2.Transportintothecytosol,Sincefattyacidsynthsistakesplaceinthecytosol,theacetylCoAproducedfrompyruvatehastobetransportedoutofthemitochondria.,citrate,oxaloacetate,pyruvate,H2OATPCO2,AcetylCoA,mitochondrion,cytosol,citrate,oxaloacetate,AcetylCoA,ATP,CoASH,ADP+Pi,malate,pyruvate,NADH+H+,NAD+,NADP+,NADPH+H+,CO2,malate,Pyrcarboxylase,Fattyacidsynthesis,PalmiticacidisthefirstsynthesizedfattyacidfromacetylCoA.Allotherfattyacidsaremadebythemodificationofpalmiticacid.,AcetylCoA,MalonylCoA,palmitate,Otherfattyacids,3.Thepathway,1）FormationofmalonylCoA,malonylCoA,Protomer(inactive),citrateisocitrate,palmitoylCoAlongchainacylCoA,Polymer(active)(10-70protomer),CH3-CACP,=,O,COA-SH,ACP-SH,Acetyltransacylase,HOOC-CH2-CSCOA,Condensation,CH3-CACP+,=,O,condensingenzyme,+CO2,Reduction,+NADPH+H+,reductase,+NADP+,Dehydration,CH3-CH-CH2-CACP,O,OH,=,=,-,C,-,dehydratase,+H2O,Reduction,-,-,=,-,32,+NADPH+H+,reductase,CH3-CH2-CH-CACP,O,=,+NADP+,ComparisonbetweenCoAandACP,Thecomparisonbetweensynthesisofpalmitateand-oxidationoffattyacid,synthesisofpalmitate-oxidationoffattyacid,1.Locationcytosolmitochondrialmatrix2.LinkedtoacylcarrierproteinCoAwith4-phosphopantetheinewith4-phosphopantetheine3.EnzymesacetylCoAcarboxylase4enzymesfattyacidsynthetase(multifunctionalenzyme)4.2CstwocarbonsfromreleasetwocarbonsasmalonylCoAacetylCoA5.CoenzymesNADPHNAD+,FAD6.ProductpalmitateacetylCoA,10.4Triacylglycerols,1.breakdownoftriacylglycerol,lipases,lipases,lipases,2.OxidationofGlycerol(Glycerolcanbemetabolizedintheliver,kidney,andintestine,butnotinadiposetissueandskeletalmuscle),end,G,NA