脂肪酸的代謝3課件

二、其他脂類的生物合成Biosynthesisofphosphatidicacid.Afattyacylgroupisactivatedbyformationofthefattyacyl–CoA,thentransferredtoesterlinkagewithL-glycerol3-phosphate,formedineitherofthetwowaysshown.PhosphatidicacidisshownherewiththecorrectstereochemistryatC-2oftheglycerolmolecule.Toconservespaceinsubsequentfigures,bothfattyacylgroupsofglycerophospholipids,andallthreeacylgroupsoftriacylglycerols,areshownprojectingtotheright.Phosphatidicacidinlipidbiosynthesis.Phosphatidicacidistheprecursorofbothtriacylglycerolsandglycerophospholipids.Themechanismsforhead-groupattachmentinphospholipidsynthesisaredescribedlaterinthissection.1.三酰甘油的合成

Insulinstimulatesconversionofdietarycarbohydratesandproteinstofat.Individualswithdiabetesmellituslackinsulin;inuncontrolleddisease,thisresultsindiminishedfattyacidsynthesis,andtheacetyl-CoAarisingfromcatabolismofcarbohydratesandproteinsisshuntedinsteadtoketonebodyproduction.Peopleinsevereketosissmellofacetone,sotheconditionissometimesmistakenfordrunkenness.RegulationoftriacylglycerolsynthesisbyinsulinGlyceroneogenesis.Thepathwayisessentiallyanabbreviatedversionofgluconeogenesis,frompyruvatetodihydroxyacetonephosphate(DHAP),followedbyconversionofDHAPtoglycerol3-phosphate,whichisusedforthesynthesisoftriacylglycerol.Regulationofglyceroneogenesis.(a)Glucocorticoidhormonesstimulateglyceroneogenesisandgluconeogenesisintheliver,whilesuppressingglyceroneogenesisintheadiposetissue(byreciprocalregulationofthegeneexpressingPEPcarboxykinase(PEPCK)inthetwotissues);thisincreasesthefluxthroughthetriacylglycerolcycle.Theglycerolfreedbythebreakdownoftriacylglycerolinadiposetissueisreleasedtothebloodandtransportedtotheliver,whereitisprimarilyconvertedtoglucose,althoughsomeisconvertedtoglycerol3-phosphatebyglycerolkinase.2.真核細(xì)胞中磷脂的合成Twogeneralstrategiesforformingthephosphodiesterbondofphospholipids.Inbothcases,CDPsuppliesthephosphategroupofthephosphodiesterbond.Initially,aheadgroup(eitherserineorglycerol3-phosphate)isattachedviaaCDPdiacylglycerolintermediate.Forphospholipidsotherthanphosphatidylserine,theheadgroupisfurthermodified,asshownhere.Intheenzymenames,PGrepresentsphosphatidylglycerol;PS,phosphatidylserine.OriginofthepolarheadgroupsofphospholipidsinE.coliTheseglycero-phospholipidsaresynthesizedusingstrategy1.Phospha-tidylglycerolissynthesizedasinbacteria.PIrepresentsphospha-tidylinositol.SynthesisofcardiolipinandphosphatidylinositolineukaryotesPathwayforphosphatidylcholinesynthesisfromcholineinmammals.Thesamestrategyshownhere(strategy2)isalsousedforsalvagingethanolamineinphosphatidylethanolaminesynthesis.Summaryofthepathwaystophosphatidyl-cholineandPhosphatidyl-ethanolamine.Conversionofphosphatidyl-ethanolaminetophosphatidyl-cholineinmammalstakesplaceonlyintheliver.真核細(xì)胞中磷脂的合成（綜合1）哺乳動(dòng)物磷脂酰膽堿和磷脂酰乙醇氨的相互轉(zhuǎn)化真核細(xì)胞中CDP-二酰甘油是合成磷脂酰肌醇，磷脂酰甘油，心磷脂的前體。3.動(dòng)物細(xì)胞中縮醛磷脂的合成4.鞘脂的生物合成由3-酮鞘氨醇合成酶催化的反應(yīng)開(kāi)始3-酮鞘氨醇二氫鞘氨醇N-脂酰二氫鞘氨醇神經(jīng)酰胺動(dòng)物細(xì)胞中糖基神經(jīng)酰胺，神經(jīng)節(jié)苷脂和鞘磷脂的由神經(jīng)酰胺合成。鞘磷脂5.花生四烯酸是合成前列腺素，血拴烷和白三烯的前體。阿斯匹林使環(huán)加氧酶失活5.膽固醇的合成HMG-CoA還原酶的活力受合成速度、降解速度及磷酸化和脫磷酸調(diào)控。甲羥戊酸到鯊烯的轉(zhuǎn)化OxidationatC-15convertsretinoltothealdehyde,retinal(c),andfurtheroxidationproducesretinoicacid(d),ahormonethatregulatesgeneexpression.Retinalcombineswiththeproteinopsintoformrhodopsin(notshown),avisualpigmentwidespreadinnature.Inthedark,retinalofrhodopsinisinthe11-cisform(c).Whenarhodopsinmoleculeisexcitedbyvisiblelight,the11-cis-retinalundergoesaseriesofphotochemicalreactionsthatconvertittoall-trans-retinal(e),forcingachangeintheshapeoftheentirerhodopsinmolecule.Thistransformationintherodcellofthevertebrateretinasendsanelectricalsignaltothebrainthatisthebasisofvisualtransduction.(a)β-CaroteneistheprecursorofvitaminA1.Isoprenestructuralunitsaresetoffbydashedredlines.Cleavageof-caroteneyieldstwomoleculesofvitaminA1(retinol)(b).

VitaminA1anditsprecursorandderivatives由鯊烯轉(zhuǎn)化為膽固醇豆甾醇麥角甾醇

膽固醇的合成是一個(gè)高度耗能的過(guò)程，合成一個(gè)膽固醇需18個(gè)乙酰輔酶A，36個(gè)ATP，16個(gè)NADPH。能源物質(zhì)過(guò)剩時(shí)，膽固醇的合成速度加快，午夜時(shí)，合成速度較快，膳食固醇類，特別是植物固醇可抑制膽固醇的合成。Lipoproteins.(a)Structureofalow-densitylipoprotein(LDL).ApolipoproteinB-100(apoB-100)isoneofthelargestsinglepolypeptidechainsknown,with4,636aminoacidresidues(Mr513,000).(b)Fourclassesoflipoproteins,visualizedintheelectronmicroscopeafternegativestaining.Clockwisefromtopleft:chylomicrons,50to200nmindiameter;VLDL,28to70nm;HDL,8to11nm;andLDL,20to25nm.脂類是由脂蛋白運(yùn)輸?shù)腖ipoproteinsandlipidtransport.(a)Lipidsaretransportedinthebloodstreamaslipoproteins,whichexistasseveralvariantsthathavedifferentfunctions,differentproteinandlipidcompositions,andthusdifferentdensities.Dietarylipidsarepackagedintochylomicrons;muchoftheirtriacylglycerolcontentisreleasedbylipoproteinlipasetoadiposeandmuscletissuesduringtransportthroughcapillaries.Chylomicronremnants(containinglargelyproteinandcholesterol)aretakenupbytheliver.EndogenouslipidsandcholesterolfromtheliveraredeliveredtoadiposeandmuscletissuebyVLDL.ExtractionoflipidfromVLDL(alongwithlossofsomeapolipoproteins)graduallyconvertssomeofittoLDL,whichdeliverscholesteroltoextrahepatictissuesorreturnstotheliver.ThelivertakesupLDL,VLDLremnants,andchylomicronremnantsbyreceptor-mediatedendocytosis.ExcesscholesterolinextrahepatictissuesistransportedbacktotheliverasHDL.Intheliver,somecholesterolisconvertedtobilesalts.(b)Bloodplasmasamplescollectedafterafast(left)andafterahigh-fatmeal(right).Chylomicronsproducedafterafattymealgivetheplasmaamilkyappearance.Reactioncatalyzedbylecithin-cholesterolacyltransferase(LCAT).ThisenzymeispresentonthesurfaceofHDLandisstimulatedbytheHDLcomponentapoA-I.CholesterylestersaccumulatewithinnascentHDLs,convertingthemtomatureHDLs.載脂蛋白在肝細(xì)胞內(nèi)質(zhì)網(wǎng)合成，在內(nèi)質(zhì)網(wǎng)組裝成脂蛋白顆粒，在高爾基體加工，包裝成分泌小泡，分泌到肝細(xì)胞外。脂蛋白顆粒的胞吞和降解LDL受體的結(jié)構(gòu)SREBPactivation.Sterolregulatoryelement-bindingproteins(SREBPs,showningreen)areembeddedintheERwhenfirstsynthesized,inacomplexwiththeproteinSREBPcleavage-activatingprotein(SCAP,red).(NandCrepresenttheaminoandcarboxylterminioftheproteins.)Whenbou