生物化學(xué)-脂類代謝

第十二章

脂類代謝

モンテレイ（メキシコ）20日AFP＝時事】最高時には體重560キロを記録したメキシコのマヌエル?ウリベさん（41）が、ギネス記録に登録されることが分かった。またウリベさんは、200キロの減量を達成した人としてもギネス記録に登録されるという。

ウリベさんはAFP通信に、「ギネス記録に最も太った人として登録されてうれしい。また、200キロも體重を減らせて幸せだ」と語った。ギネス記録はウリベさんを最も體重が重い人として認定し、2008年版でウリベさんの寫真を載せ、治療の過程なども紹介する。KeyTerms

triacylglycerol(neutralfat,triacylglyceride)bilesaltchylomicronacyl

adenylatecarnitineb-oxidationpathwayvitaminB12(cobalamin)peroxisomeketonebodyacylcarrierprotein(ACP)fattyacidsynthasemalonyl

CoAacetylCoA

carboxylasemegasynthasepolyketidenonribosomalpeptideAMP-dependentproteinkinase(AMPK)proteinphosphatase2AarachidonateprostaglandineicosanoidII.TransducingAnOverviewofFattyAcidMetabolismFattyaciddegradationandsynthesisarerelativelysimpleprocessesthatareessentiallythereverseofeachother.Theprocessofdegradationconvertsanaliphaticcompoundintoasetofactivatedacetylunits(acetylCoA)thatcanbeprocessedbythecitricacidcycle(Figure22.2).Anactivatedfattyacidisoxidizedtointroduceadoublebond;thedoublebondishydratedtointroduceanoxygen;thealcoholisoxidizedtoaketone;and,finally,thefourcarbonfragmentiscleavedbycoenzymeAtoyieldacetylCoAandafattyacidchaintwocarbonsshorter.Ifthefattyacidhasanevennumberofcarbonatomsandissaturated,theprocessissimplyrepeateduntilthefattyacidiscompletelyconvertedintoacetylCoAunits.Fattyacidsynthesisisessentiallythereverseofthisprocess.Becausetheresultisapolymer,theprocessstartswithmonomersinthiscasewithactivatedacylgroup(mostsimply,anacetylunit)andmalonylunits(seeFigure22.2).Themalonylunitiscondensedwiththeacetylunittoformafour-carbonfragment.Toproducetherequiredhydrocarbonchain,thecarbonylmustbereduced.Thefragmentisreduced,dehydrated,andreducedagain,exactlytheoppositeofdegradation,tobringthecarbonylgrouptothelevelofamethylenegroupwiththeformationofbutyryl

CoA.AnotheractivatedmalonylgroupcondenseswiththebutyrylunitandtheprocessisrepeateduntilaC16fattyacidissynthesizedTriacylglycerolsAreHighlyConcentratedEnergyStoresFattyacidsarephysiologicallyimportantas(1)componentsofphospholipidsandglycolipids,(2)hydrophilicmodifiersofproteins,(3)fuelmolecules,and(4)hormonesandintracellularmessengers.Theyarestoredinadiposetissueas

triacylglycerols(neutralfat).一脂類的生理功能☆構(gòu)成細胞膜的必要成分☆氧化供能：9克葡萄糖≈1克脂肪？☆其他功能：

保持體溫

保護，固定內(nèi)臟

膽固醇是生成膽汁酸，VD3，類固醇激素的原料

H3C-（CH2）n-C-C-C=O-OH脂肪酸的通式：

Triacylglycerols

arehighlyconcentratedstoresofmetabolicenergybecausetheyarereducedandanhydrous.Theyieldfromthecompleteoxidationoffattyacidsisabout9kcalg-1(38kJg-1),incontrastwithabout4kcalg-1(17kJg-1)forcarbohydratesandproteins.Thebasisofthislargedifferenceincaloriyieldisthatfattyacidsaremuchmorereduced.Furthermore,triacylglycerolsarenonpolar,andsotheyarestoredinanearlyanhydrousform,whereasmuchmorepolarproteinsandcarbohydratesaremorehighlyhydrated.Infact,1gofdryglycogenbindsabout2gofwater.Consequently,agramofnearlyanhydrousfatstoresmorethansixtimesasmuchenergyasagramofhydratedglycogen,whichislikelythereasonthattriacylglycerolsratherthanglycogenwereselectedinevolutionasthemajorenergyreservoir.Theglycogenandglucosestoresprovideenoughenergytosustainbiologicalfunctionforabout24hours,whereasthetriacylglycerolstoresallowsurvivalforseveralweeks.TriacylglycerolsAreHighlyConcentratedEnergyStoresTheutilityoftriacylglycerolsasanenergysourceisdramaticallyillustratedbytheabilitiesofmigratorybirds,whichcan

flygreatdistanceswithouteating.ExamplesaretheAmericangoldenploverandtheruby-throatedsparrow.ThegoldenploverfliesfromAlaskatothesoutherntipofSouthAmerica;alargesegmentoftheflight(3800km,or2400miles)isoveropenocean,wherethebirdscannotfeed.Theruby-throatedhummingbirdcanflynonstopacrosstheGulfofMexico.Fattyacidsprovidetheenergysourceforboththeseprodigiousfeats.Inmammals,themajorsiteofaccumulationoftriacylglycerolsisthecytoplasmofadiposecells(fatcells).Dropletsoftriacylglycerolcoalescetoformalargeglobule,whichmayoccupymostofthecellvolume(seeFigure22.1).Adiposecellsarespecializedforthesynthesisandstorageoftriacylglycerolsandfortheirmobilizationintofuelmoleculesthataretransportedtoothertissuesbytheblood.

脂肪酸+甘油形成的酯根據(jù)結(jié)合的脂肪酸分子數(shù)目又分為：單（脂）酰甘油；二（脂）酰甘油；三（脂）酰甘油：甘油三酯/脂肪

二脂類的降解☆脂肪的水解：

☆甘油的代謝：

★脂肪酸的分解代謝：激素敏感酯酶TriacylglycerolsAreHydrolyzedbyCyclicAMP-RegulatedLipasesTriacylglycerolsinadiposetissueareconvertedintofreefattyacidsandglycerolforreleaseintothebloodstreaminresponsetohormonalsignals.Ahormone-sensitivelipaseinitiatestheprocess.TheUtilizationofFattyAcidsasFuelRequiresThreeStagesofProcessingPeripheraltissuesgainaccesstothelipidenergyreservesstoredinadiposetissuethroughthreestagesofprocessing.First,thelipidsmustbemobilized.Inthisprocess,triacylglycerolsaredegradedtofattyacidsandglycerol,whichare

releasedfromtheadiposetissueandtransportedtotheenergy-requiringtissues.Second,atthesetissues,thefattyacids

mustbeactivatedandtransportedintomitochondriafordegradation.Third,thefattyacidsarebrokendowninastep-bystep

fashionintoacetylCoA,whichisthenprocessedinthecitricacidcycle.激活的腺苷酸環(huán)化酶激活的蛋白激酶激活的酯酶甘油生成3-磷酸甘油后進一步生成

磷酸二羥丙酮進入糖酵解途徑甘油還可以生成葡萄糖（糖異生）☆甘油的代謝：

←糖酵解

甘油磷酸二羥丙酮葡萄糖←☆脂肪酸的-氧化

AcetylCoA,NADH,andFADH2AreGeneratedinEachRoundofFattyAcidOxidationFattyAcidsAreLinkedtoCoenzymeABeforeTheyAreOxidized

脂肪酸的活化（線粒體外膜）脂酰CoA轉(zhuǎn)運入線粒體肉堿╋

脂酰CoA

→脂酰肉堿

轉(zhuǎn)運至線粒體基質(zhì)中

脂酰肉堿→脂酰CoA

╋肉堿

肉堿→脂酰肉堿脂肪酸-氧化反應(yīng)

1904年F.Knoop

的研究證明：

脂肪酸通過連續(xù)除去二碳單位

而降解FattyAcidMetabolism脫氫→水化→脫氫→硫解→

脂肪酸-氧化的反應(yīng)過程

脂肪酸-氧化→乙酰COA→TCA循環(huán)

NADH,FADH2→電子傳遞鏈氧化磷酸化活化時消耗兩分子ATP，凈生成

129分子ATP

。

三16碳的棕櫚酸徹底氧化

131個ATPOdd-ChainFattyAcidsYieldPropionylCoenzymeAintheFinalThiolysisStep

Fattyacidshavinganoddnumberofcarbonatomsareminorspecies.Theyareoxidizedinthesamewayasfattyacidshavinganevennumber,exceptthatpropionyl

CoAandacetylCoA,ratherthantwomoleculesofacetylCoA,areproducedinthefinalroundofdegradation.Theactivatedthree-carbonunitinpropionyl

CoAentersthecitricacidcycleafterithasbeenconvertedintosuccinyl

CoA四奇數(shù)碳原子脂肪酸的氧化丙酸→丙酰COA→琥珀酰COA→TCA循環(huán)

硫激酶丙酸－－→丙酰COA

ATP→AMP

丙酰COA羧化酶丙酰-COA

－－→D-甲基丙二酸單酰COA

ATP→ADPD-甲基丙二酸單酰COA→→琥珀酰COA

Odd-ChainFattyAcidsYieldPropionylCoenzymeAintheFinalThiolysisStep

Fattyacidshavinganoddnumberofcarbonatomsareminorspecies.Theyareoxidizedinthesamewayasfattyacidshavinganevennumber,exceptthatpropionyl

CoAandacetylCoA,ratherthantwomoleculesofacetylCoA,areproducedinthefinalroundofdegradation.Theactivatedthree-carbonunitinpropionyl

CoAentersthecitricacidcycleafterithasbeenconvertedintosuccinyl

CoA.丙酰COA琥珀酰COA五酮體(KetoneBodies)

KetoneBodiesAreFormedfromAcetylCoenzymeAWhenFatBreakdownPredominates丙酮?-羥丁酸乙酰乙酸前體；乙酰CoA

肝中生成肝外組織分解分解產(chǎn)物；乙酰CoA

FormationofKetoneBodies.

TheKetonebodies-acetoacetate,d-3-hydroxybutyrate,andacetonefromacetylCoAareformedprimarilyintheliver.Enzymescatalyzingthesereactionsare(1)3-ketothiolase,(2)hydroxymethylglutaryl

CoA

synthase,(3)hydroxymethylglutaryl

CoAcleavageenzyme,and

(4)d-3-hydroxybutyratedehydrogenase.Acetoacetatespontaneouslydecarboxylatestoformacetone.AcetoacetatecanbeconvertedintotwomoleculesofacetylCoA,whichthenenterthecitricacidcycle.KetoneBodiesAreaMajorFuelinSomeTissuesThemajorsiteofproductionofacetoacetateand3-hydroxybutyrateistheliver.Thesesubstancesdiffusefromthelivermitochondriaintothebloodandaretransportedtoperipheraltissues.Theseketonebodieswereinitiallyregardedasdegradationproductsoflittlephysiologicalvalue.However,theresultsofstudiesbyGeorgeCahillandothersrevealedthatthesederivativesofacetylCoAareimportantmoleculesinenergymetabolism.Acetoacetateand3-hydroxybutyratearenormalfuelsofrespirationandarequantitativelyimportantassourcesofenergy.Indeed,heartmuscleandtherenalcortexuseacetoacetateinpreferencetoglucose.Incontrast,glucoseisthemajorfuelforthebrainandredbloodcellsinwell-nourishedpeopleonabalanceddiet.However,thebrainadaptstotheutilizationofacetoacetateduringstarvationanddiabetes(Sections30.3.1and30.3.2).Inprolongedstarvation,75%ofthefuelneedsofthebrainaremetbyketonebodies.AnimalsCannotConvertFattyAcidsintoGlucose

Itisimportanttonotethatanimalsareunabletoeffectthenetsynthesisofglucosefromfattyacids.Specifically,acetylCoAcannotbeconvertedintopyruvateoroxaloacetateinanimals.ThetwocarbonatomsoftheacetylgroupofacetylCoAenterthecitricacidcycle,buttwocarbonatomsleavethecycleinthedecarboxylationscatalyzedbyisocitrate

dehydrogenaseanda-ketoglutarate

dehydrogenase.Consequently,oxaloacetateisregenerated,butitisnotformeddenovowhentheacetylunitofacetylCoAisoxidizedbythecitricacidcycle.Incontrast,plantshavetwoadditionalenzymesenablingthemtoconvertthecarbonatomsofacetylCoAintooxaloacetate.六脂肪酸的生物合成

（16C棕櫚酸）合成前體：乙酰CoA

反應(yīng)部位：細胞質(zhì)1.乙酰COA的轉(zhuǎn)運

由線粒體轉(zhuǎn)運至細胞質(zhì)）

2.乙酰CoA的羧化

乙酰COA→丙二酸單酰COA3.脂肪酸鏈的合成（分為三階段行）：☆?；霓D(zhuǎn)移：乙?；D(zhuǎn)移到中央巰基上再轉(zhuǎn)移到外圍巰基上☆脂肪酸鏈的延伸：縮合，還原，脫水，還原☆

脂酰基的水解：硫解酶乙酰COA的轉(zhuǎn)運TransferofAcetylCoAtotheCytosol.AcetylCoAistransferredfrommitochondriatothecytosol,andthereducingpotentialNADHisconcomitantlyconvertedintothatofNADPHbythisseriesofreactions.乙酰COA羧化酶丙二酸單酰COATheFormationofMalonylCoenzymeAIstheCommittedStepinFattyAcidSynthesisIntermediatesinFattyAcidSynthesisAreAttachedtoanAcylCarrierProteinTheElongationCycleinFattyAcidSynthesisFattyAcidSynthesis.Fattyacidsaresynthesizedbytherepetitionofthefollowingreactionsequence:condensation,reduction,dehydration,andreduction.Theintermediatesshownhereareproducedinthefirstroundofsynthesis.II.TransducingandStoringEnergy22.FattyAcidMetabolism22.4.FattyAcidsAreSynthesizedandDegradedbyDifferentPathways?；霓D(zhuǎn)移：乙酰基轉(zhuǎn)移到中央巰基上再轉(zhuǎn)移到外圍巰基上

☆乙酰COA+?；d體蛋白(ACP)→乙酰-ACP☆丙二酸單酰COA

+酰基載體蛋白(ACP)→丙二酸單酰-ACP

脂肪酸合成酶復(fù)合體包括六種酶和一種?；d體蛋白(ACP)。各種生物脂肪酸合成過程相似，脂肪酸和酶系統(tǒng)均有上述六種酶和一種酰基載體蛋白組成，但合酶系統(tǒng)的組裝形式不同。大腸桿菌中，上述6種酶以ACP為中心，有序地組成松散的多酶復(fù)合體。動物中，上述6種酶，ACP和1種棕櫚酰-ACP硫脂酶7種功能集于一條肽鏈酶系統(tǒng)為含2個相同亞基的2聚體。單聚體無活性。棕櫚酰-ACP硫脂酶只有在合成16碳的脂肪酸鏈后才有活性。其他生物缺乏此酶。酰基載體蛋白(ACP)?；D(zhuǎn)移酶（AT）

-丙二酸單酰轉(zhuǎn)移酶（MT）

-酮脂酰ACP合成酶（KS）

-酮脂酰ACP還原酶（KR）-羥脂酰ACP脫水酶（HD）

烯脂酰ACP還原酶（ER）FattyAcidSynthaseInhibitorsMayBeUsefulDrugs

Fattyacidsynthaseisoverexpressedinsomebreastcancers.Researchersintriguedbythisobservationhavetestedinhibitorsoffattyacidsynthaseonmicetoseehowtheinhibitorsaffecttumorgrowth.Astartlingobservationwasmade:micetreatedwithinhibitorsofthecondensingenzymeshowedremarkableweightlossduetoinhibitionoffeeding.Theresultsofadditionalstudiesrevealedthatthisinhibitionisdue,atleastinpart,totheaccumulationofmalonyl

CoA.Thus,fattyacidsynthaseinhibitorsareexcitingcandidatesbothasantitumorandasantiobesitydrugs.AcetylCoenzymeACarboxylasePlaysaKeyRoleinControllingFattyAcidMetabolism

Fattyacidmetabolismisstringentlycontrolledsothatsynthesisanddegradationarehighlyresponsivetophysiologicalneeds.Fattyacidsynthesisismaximalwhencarbohydrateandenergyareplentifulandwhenfattyacidsarescarce.AcetylCoA

carboxylaseplaysanessentialroleinregulatingfattyacidsynthesisanddegradation.Recallthatthisenzymecatalyzesthecommittedstepinfattyacidsynthesis:theproductionofmalonyl

CoA(theactivatedtwo-carbondonor).Thecarboxylaseiscontrolledbythreeglobalsignalsglucagon,epinephrine,andinsulinthatcorrespondtotheoverallenergystatusoftheorganism.Insulinstimulatesfattyacidsynthesisbyactivatingthecarboxylase,whereasglucagonandepinephrinehavethereverseeffect.Thelevelsofcitrate,palmitoyl

CoA,andAMPwithinacellalsoexertcontrol.Citrate,asignalthatbuildingblocksandenergyareabundant,activatesthecarboxylase.Palmitoyl

CoAandAMP,incontrast,leadtotheinhibitionofthecarboxylase.Thus,thisimportantenzymeissubjecttobothglobalandlocalregulation.Wewillexamineeachoftheselevelsofregulationinturn.∣∣SHSHACP上有一個活性巰基（中央巰基），-酮脂酰-ACP合酶上也有一個活性巰基（外圍巰基）大腸桿菌脂肪酸合酶ACP:Ser殘基上連有:

4-磷酸泛酰巰基乙胺↙縮合

→

還原

→

脫水

→

還原

→脂肪酸鏈的延伸：縮合，還原，脫水，還原脂?；乃猓毫蚪饷浮?/p>

-酮脂酰合成酶（KS）對2C至14C的酰基ACP均有很高活性,而對16C的棕櫚酰ACP活性很低?！钭貦磅?ACP硫脂酶只有在合成16碳的脂肪酸鏈后才有活性。棕櫚酰-ACP硫脂酶七脂肪酸代謝調(diào)控快速調(diào)節(jié)；

檸檬酸激活乙酰CｏA羧化酶棕櫚酰CoA抑制乙酰CｏA羧化酶緩慢調(diào)節(jié)

基因調(diào)控→動物飼喂低脂肪飼料時

乙酰CｏA羧化酶脂肪合成酶含量升高八脂肪酸合成與分解的差別區(qū)別點

脂肪酸合成脂肪酸-氧化反應(yīng)部位:

細胞質(zhì)線粒體酶7種多酶復(fù)合體4種酶、是否多酶合體不明

輔酶NADPHFNDH

２

NADH二氫單位

丙二酸單酰輔酶A乙酰輔酶A載體ACP輔酶底物轉(zhuǎn)運檸檬酸穿梭作用肉堿轉(zhuǎn)運循環(huán)次數(shù)7次7次反應(yīng)方向從甲基端向羧基端由羧基端開始降解羥脂酰基的立體結(jié)構(gòu)D型L型能量消耗7個ATP14個NADPH產(chǎn)生129個ATPFattyAcidsAreSynthesizedandDegradedbyDifferentPathways

ConceptualInsights,OverviewofCarbohydrateandFattyAcidMetabolism,willhelpyouunderstandhowfattyacidmetabolismfitsinwithotherenergystorageandutilizationpathways(glycolysis,citricacidcyclem,pentosephosphatepathwaym,glycogenmetabolism),withafocusoncarbonandenergyflux.Fattyacidsynthesisisnotsimplyareversalofthedegradativepathway.Rather,itconsistsofanewsetofreactions,againexemplifyingtheprinciplethatsyntheticanddegradativepathwaysarealmostalwaysdistinct.Someimportantdifferencesbetweenthepathwaysare:1.Synthesistakesplaceinthecytosol,incontrastwithdegradation,whichtakesplaceprimarilyinthemitochondrialmatrix.2.Intermediatesinfattyacidsynthesisarecovalentlylinkedtothesulfhydrylgroupsofanacylcarrierprotein(ACP),whereasintermediatesinfattyacidbreakdownarecovalentlyattachedtothesulfhydrylgroupofcoenzymeA.3.Theenzymesoffattyacidsynthesisinhigherorganismsarejoinedinasinglepolypeptidechaincalledfattyacidsynthase.Incontrast,thedegradativeenzymesdonotseemtobeassociated.4.Thegrowingfattyacidchainiselongatedbythesequentialadditionoftwo-carbonunitsderivedfromacetylCoA.TheactivateddonoroftwocarbonunitsintheelongationstepismalonylACP.TheelongationreactionisdrivenbythereleaseofCO2.5.ThereductantinfattyacidsynthesisisNADPH,whereastheoxidantsinfattyaciddegradationareNAD+andFAD.6.Elongationbythefattyacidsynthasecomplexstopsonformationofpalmitate

(C16).Furtherelongationandtheinsertionofdoublebondsarecarriedoutbyotherenzymesystems.脂肪酸分解脂肪酸合成九糖代謝為脂肪合成提供所有的原料甘油乙酰CoANADPH（檸檬酸穿梭，磷酸戊糖途徑）ATP十脂類的運輸☆游離脂肪酸（Freefattyacids、ＦＦＡ）與清蛋白形成復(fù)合體運輸☆中性脂肪，膽固醇，膽固醇酯，磷脂與蛋白質(zhì)結(jié)合成脂蛋白(lipoprotein)形式運輸。四種脂蛋白乳糜微粒（CM）極低密度脂蛋白（VLDL）低密度脂蛋白（LDL）高密度脂蛋白（HDL）SiteofCholesterolSynthesis.Electronmicrographofapartofalivercellactivelyengagedinthe

synthesisandsecretionofverylowdensitylipoprotein(VLDL).Thearrowpointstoavesiclethatisreleasingitscontent

ofVLDLparticles.[CourtesyofDr.GeorgePalade.]極低密度脂蛋白（VLDL）SchematicModelofLow-DensityLipoprotein.TheLDLparticleisapproximately22nm(220?)in

diameter.低密度脂蛋白（LDL）膽固醇含量高中性脂肪含量高EndocytosisofLDLBoundtoItsReceptor.

(A)ElectronmicrographshowingLDL(conjugatedto

ferritinforvisualization,darkspots)boundtoacoated-pitregiononthesurfaceofaculturedhumanfibroblastcell.(B)

Micrographshowingthisregioninvaginatingandfusingtoformanendocyticvesicle[FromR.G.W.Anderson,M.S.

Brown,andJ.L.Goldstein.Cell10(1977):351.]

III.SynthesizingtheMoleculesofLife26.TheBiosynthesisofMembraneLipidsandSteroids26.3.TheComplexRegulationofCholesterolBiosynthesisTakesPlaceatSeveralLevels

低密度脂蛋白（LDL）受體十一脂肪代謝調(diào)控☆脂肪組織中的脂肪代謝調(diào)控☆糖代謝與脂肪代謝的調(diào)控脂肪組織中的脂肪代謝調(diào)控脂肪在組織中無甘油激酶，故不能利用游離的甘油作為脂肪合成的原料，只能靠糖代謝產(chǎn)生的磷酸二羥丙酮轉(zhuǎn)變?yōu)?-磷酸甘油。因此脂肪組織中的脂肪代謝受血糖的調(diào)控。當(dāng)血糖升高時，脂肪組織中的3-磷酸甘油含量高，脂肪合成速度加快，血糖下降時，脂肪合成反應(yīng)減慢，分解反應(yīng)加快由此而產(chǎn)生的游離脂肪酸，進入血中，組織細胞利用。CholesterolIsaLipidBasedonaSteroidNucleus

Cholesterolisalipidwithastructurequitedifferentfromthatofphospholipids.Itisasteroid,builtfromfourlinked

hydrocarbonrings.Ahydrocarbontailislinkedtothesteroidatoneend,andahydroxylgroupisattachedattheotherend.Inmembranes,themoleculeisorientedparalleltothefattyacidchainsofthephospholipids,andthehydroxylgroupinteractswiththe

nearbyphospholipidheadgroups.Cholesterolisabsentfromprokaryotesbutisfoundtovaryingdegreesinvirtuallyall

animalmembranes.Itconstitutesalmost25%ofthemembranelipidsincertainnervecellsbutisessentiallyabsentfrom

someintracellularmembranes.CholesterolCarbonNumbering.

Thenumberingschemeforthecarbonatomsincholesterolandother

steroids.

膽固醇☆2碳的乙酸→30碳的鯊烯→27碳的膽固醇→21碳的孕酮→19碳的睪酮→18碳的雌二醇。膽固醇是孕酮，睪酮以及雌二醇等類固醇激素的前提。膽固醇還可以生成膽酸及其衍生物，VD等生物活性物質(zhì)CholesterolIsSynthesizedfromAcetylCoenzymeAinThreeStagesCholesterolisasteroidcomponentofeukaryoticmembranesandaprecursorofsteroidhormones.Thecommittedstepinitssynthesisistheformationofmevalonatefrom3-hydroxy-3-methylglutarylCoA(derivedfromacetylCoAandacetoacetyl

CoA).Mevalonateisconvertedintoisopentenylpyrophosphate(C5),whichcondenseswithitsisomer,dimethylallylpyrophosphate(C5),toformgeranylpyrophosphate(C10).Theadditionofasecondmoleculeofisopentenylpyrophosphateyieldsfarnesylpyrophosphate(C15),whichcondenseswithitselftoformsqualene(C30).Thisintermediatecyclizestolanosterol(C30),whichismodifiedtoyieldcholesterol(C27).SchematicStructureofaPhospholipid.

乙醛酸循環(huán)乙酰COA乙醛酸↘↙異檸檬酸裂解酶蘋果酸合酶乙醛酸循環(huán)乙醛酸循環(huán)可以看作是檸檬酸循環(huán)的一個支路，它實際上繞過了檸檬酸循環(huán)的兩步脫羧反應(yīng)。乙醛酸循環(huán)中異檸檬酸裂解酶和蘋果酸合酶兩個關(guān)鍵每外其余的每均與檸檬酸循環(huán)相同。乙醛酸循環(huán)不存在于動物及高等植物的營養(yǎng)器官中，而存在于一些細菌，藻類及高等植物種子的乙醛酸體中（glyoxysome）Summary

TriacylglycerolsAreHighlyConcentratedEnergyStoresFattyacidsarephysiologicallyimportantas(1)componentsofphospholipidsandglycolipids,(2)hydrophilicmodifiersofproteins,(3)fuelmolecules,and(4)hormonesandintracellularmessengers.Theyarestoredinadiposetissueastriacylglycerols(neutralfat).TheUtilizationofFattyAcidsasFuelRequiresThreeStagesofProcessingTriacylglycerolscanbemobilizedbythehydrolyticactionoflipasesthatareunderhormonalcontrol.Fattyacidsareactivatedtoacyl

CoAs,transportedacrosstheinnermitochondrialmembranebycarnitine,anddegradedinthemitochondrialmatrixbyarecurringsequenceoffourreactions:oxidationbyFAD,hydration,oxidationbyNAD+,andthiolysisbyCoA.TheFADH2andNADHformedintheoxidationstepstransfertheirelectronstoO2bymeansoftherespiratorychain,whereastheacetylCoAformedinthethiolysisstepnormallyentersthecitricacidcyclebycondensingwithoxaloacetate.Mammalsareunabletoconvertfattyacidsintoglucose,becausetheylackapathwayforthenetproductionofoxaloacetate,pyruvate,orothergluconeogenicintermediatesfromacetylCoA.CertainFattyAcidsRequireAdditionalStepsforDegradation

Fattyacidsthatcontaindoublebondsoroddnumbersofcarbonatomsrequireancillarystepstobedegraded.Anisomeraseandareductasearerequiredfortheoxidationofunsaturatedfattyacids,whereaspropionyl

CoAderivedfromchainswithoddnumbersofcarbonsrequiresavitaminB12-dependentenzymetobeconvertedintosuccinyl

CoA.FattyAcidsAreSynthesizedandDegradedbyDifferentPathways

Fattyacidsaresynthesizedinthecytosolbyadifferentpathwayfromthatofboxidation.SynthesisstartswiththecarboxylationofacetylCoAtomalonyl

CoA,thecommittedstep.ThisATP-drivenreactioniscatalyzedbyacetylCoA

carboxylase,abiotinenzyme.Theintermediatesinfattyacidsynthesisarelinkedtoanacylcarrierprotein.AcetylACPisformedfromacetylCoA,andmalonylACPisformedfrommalonyl

CoA.AcetylACPandmalonylACPcondensetoformacetoacetylACP,areactiondrivenbythereleaseofCO2fromtheactivatedmalonylunit.Areduction,adehydration,andasecondreductionfollow.NADPHisthereductantinthesesteps.ThebutyrylACPformedinthiswayisreadyforasecondroundofelongation,startingwiththeadditionofatwo-carbonunitfrommalo