Lipidmetabolism脂类代谢课件

10.LipidmetabolismHuangxiaoLinyiuniversityKeynotesStructuresandrolesoffattyacidsFattyacidbreakdownFattyacidsynthesisTriacylglycerols10.1Structuresandrolesoffattyacids

Fattyacidshavealonghydrocarbonchainwithaterminalcarboxylicacidgroup.Mostfattyacidshaveanevennumberofcarbonatomsinanunbranchedchain.Saturatedfattyacidshavenodoublebondsbetweenthecarbonatoms,whereasmono-andpolyunsaturatedfattyacidshaveoneormoredoublebonds.Fattyacidshavefourmajorbiologicalroles:1)Theyarecomponentsofmembranes(glycerophospholipidsandsphingolipids)2)Severalproteinsarecovalentlymodifiedbyfattyacids.3)Theyactasenergystores(triacylglycerols)andfuelmolecules.4)Fattyacidderivativesserveashormonesandintracellularsecondmessengers.10.2FattyacidbreakdownOverviewActivationTransportintomitochondriaβ-oxidationpathwayEnergyyieldKetonebodies1.overviewFattyacidbreakdownbringsabouttheoxidationoflong-chainfattyacids.ThefattyacidsarefirstconvertedtotheiracylcoenzymeAderivativesandthendegradedbythesuccessiveremovaloftwo-carbonunitsfromtheendofthefattyacidasacetylCoA.

RCOOH+CoA—SHRCO~SCoAAcylCoAsynthetase

ATPAMP+PPiMg2+

H2O2PithereactionisirreversiblefattyacidacylCoA3.Transportintomitochondria

longerchainacylCoAsdonotreadilycrosstheinnermitochondrialmembrane,andrequireaspecifictransportmechanism.RCO-SCoACoA-SHtransferase(CH3)3N+-CH2CH-CH2COOHOHcarnitine(CH3)3N+CH2CHCH2COOHRCO-Oacylcarnitine

R-COSCoA

H-SCoAcarnitineR-CO-carnitine

R-CO-carnitine

H-SCoA

carnitine

R-COSCoA

transferaseⅠβ-oxidationtransferaseⅡInnermitochondrialmembrane4.β-OxidationpathwayOxidation(byFAD)HydrationOxidation(byNAD+)Thiolysis

①

oxidation

acylCoAdehydrogenaseFADFADH2②

hydration

RCH2CCCO~CoAHH

trans2-enoylCoA

enoylCoAhydratase

H2OOHRCH2CHCH2CO~SCoA3-hydroxyacylCoA1.5ATPrespiratorychainＯR-CH2-

CH2C-SCoA||OHRCH2CHCH2CO~SCoA

③

oxidation

NAD+NADH+H+dehydrogenase④

thiolysis

CH3CO~SCoA

RCH2CO~SCoA

（1）（2）（3）（4）3-ketoacylCoARCH2C~SCoAOCH2COCoA-SHketothiolase

2.5ATPrespiratorychain

roundreaction

Oxidationofodd-chainfattyacidRacemaseB12CH3-CH2-COCoAPropionylCoAHOOC-CH2-CH2-COCoASuccinylCoA5.Energyyield(C16:0)

PalmitoylCoA+7FAD+7NAD++7CoA-SH+7H2O→8acetylCoA+7FADH2+7(NADH+H+)PalmitoylCoA+7FAD+7CoA+7H2O7Reactioncyclesof-Oxidation8acetylCoA+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)ATPsproduced1.FrompalmitatetopalmitoylCoAconsumed2ATPs

Doyouthinkthattheyoungmantakes250gofbutterperdayfor3days?Really!Oh,soStupid!theremustbelotsofketonebodiesinhisurine

10.3FattyacidsynthesisOverviewTransportintothecytosolThepathway1.Overview

Fattyacidsynthesisinvolvesthecondensationoftwo-carbonunits,intheformofacetylCoA,toformlonghydrocarbonchainsinaseriesofreactions.citrateoxaloacetatepyruvateH2OATPCO2AcetylCoA

mitochondrioncytosol

citrateoxaloacetateAcetylCoAATP,CoASHADP+Pi

malatepyruvateNADH+H+NAD+NADP+NADPH+H+CO2malate

PyrcarboxylaseFattyacidsynthesis

PalmiticacidisthefirstsynthesizedfattyacidfromacetylCoA.Allotherfattyacidsaremadebythemodificationofpalmiticacid.AcetylCoAMalonylCoApalmitateOtherfattyacids①②③

3.Thepathway

CondensationCH3-C～ACP+=OHOOC-CH2-C～ACPO=

condensingenzymeCH3-C-CH2-C～ACPO=O=+CO2

ReductionCH3-C-CH2-C～SACPO=O=+NADPH++

H+

reductaseCH3-CH-CH2-C～ACPO-OH=+NADP+

DehydrationCH3-CH-CH2-C～ACPO

︱OH==-C-C==CO-CH3-HH～ACP

dehydratase+H2O

Reduction-C==CO-CH3HH～ACPC-=-

32+NADPH+H+

reductaseCH3-CH2-CH-C～ACPO=+NADP+

C==CO-CH3-HH

ComparisonbetweenCoAandACPThecomparisonbetweensynthesisofpalmitateand-oxidationoffattyacidsynthesisofpalmitate-oxidationoffattyacid

1.Locationcytosolmitochondrialmatrix2.LinkedtoacylcarrierproteinCoA

with4-phosphopantetheinewith4-phosphopantetheine3.EnzymesacetylCoAcarboxylase4enzymesfattyacidsynthetase(multifunctionalenzyme)4.2CstwocarbonsfromreleasetwocarbonsasmalonylCoAacetylCoA5.CoenzymesNADPHNAD+,FAD6.ProductpalmitateacetylCoA10.4Triacylglycerols

1.breakdownoftriacylglycerollipaseslipas