文件生物化學(xué)

UtilizationandUtilizationandTransportofFatandOverviewofmetabolismwithfattyacidand17-Lipid:usually5%--25%Lipid:usually5%--25%ofbodyweightforanormalmammal;InrealitytheupperboundismuchhigherProvideasmuchas80%ofenergysupplyforcertaintissuessuchasliverandheart.FreeFattyAcidTotal#ofTotal#ofCountingfromTriglyceride(三酸甘油酯;Triglyceride(三酸甘油酯;Othernames:triacylglycerol;alsocalledConstituteasmuchas90%totallipidstoredinadipose由一個甘油分子(glycerol)和三個脂肪酸分子(fattyacid)組Simplefat:allthethreefattyacidsaretheMixedfat:nottheAsimpleorganicmoleculesuchascholine(膽堿)?isacomponentof?isacomponentofmanyanimal?ItinfluencesmembranefluiditybyitsbulkyBecausetheringstructureofcholesterolisratherrigid,whichreducesfluidity.?ItalsocausesItItalsoexistsasacholesterolester,whichismoreAfterameal,Afterameal,about500mglipidper100mlof100mg220mg160mg…500FatisFatismoreefficientafuelthanBecauseinfattherearemoreCH2andCH3groupswhicharemorereduced.TheycanthusbeprocessedbyO2longer(比較經(jīng)燒)。Fat:Carbohydrate:17MorescientificCO2Respiratoryquotient(RQ)MorescientificCO2Respiratoryquotient(RQ)6RQ=RQ=6FatismoreFatismoreefficientafuelthanFatishydrophobicandsugaris1gramfatcontains1gramfat實打?qū)?gramglycogencontains1/3gwateronly2/3gglucose（層層摻水So，fatissixfoldmoreefficientthan37x3/17≈HibernationrequiresHibernationrequiresmigrationrequiresfatInflightUtilizationandTransportofUtilizationandTransportofFatand1.Afterameal,dietaryfatisbrokendownintofreefattyacids(FFAs)andmonoglyceridesbypancreaticlipase,inordertobeabsorbedbythe2.Onceacrosstheintestinalbarrier,theyarereformedintotriglyceridesandpackagedintochylomicron(sothattheybecomesoluble).Chylomicron:anoildropletcoatedwithmorepolarlipidsandaskinofprotein,whichhelpdisperseandpartiallysolubilizethefatfortransporttotissues.3.Theyarethenprimarilyabsorbedbyadiposetissues.HowtoHowtolipoproteinlipase(LPL)inthecapillariesadiposetissueshydrolysesreleasedaretakenupintotheadipocytesforstorage.Howtolipoproteinlipase(LPL)inthecapillariesadiposetissueshydrolysesreleasedaretakenupintotheadipocytesforstorage.remnantsintothevariouslipoproteinvery-low-(VLDLs),whicharethentransportedtothebloodandthentoperipheraltissues.3.Inperipheraltissues,LPLsdigestpartoftheVLDL(byremovingtriglycerides)intoIDLandFFAs.FFAscanthenbeabsorbedbytissues.ThereareotherthingslikeVLDL,LDL,TheyarecalledLipoproteins:transferfatLipoproteins:transferfattodensityThelowerlipidcontent,thehigherBindingofaBindingofachylomicrontolipoproteinlipaseontheinnersurfaceofaThechylomicronisanchoredbylipoproteinlipase,whichislinkedbyapolysaccharidechaintothelumenalsurfaceoftheendothelialcell.WhenactivatedbyapoproteinC-II,thelipasehydrolyzesthetriacylglycerolsinthechylomicron,producingglycerolandfreefattyacids.Somefattyacidareabsorbedbynearbycells,whileothers,stillratherinsoluble,becomecomplexedwithserumalbuminfortransporttomoredistantcells.?Afterabsorptionintothe?Afterabsorptionintothecell,fattycanbeeithercatabolizedtogenerateenergyorinadiposecells,usedtoresynthesize?BecauseadipocyteslackglycerolGlycerol-3-phosphateforre-synthesisoftriglyceridemustcomefromglycolysis.GlycerolpathwayreducingDHAPtoglycerol-3-phosphate(G3P)byG3Pdehydrogenase,followedbydephosphorylationtoglycerolbyglycerol-3-phosphateDonotglycerol-3-phosphateDonotconfuseOverviewoflipoproteintransportpathwaysOverviewoflipoproteintransportpathwaysand1.Chylomicronsaredegradedintochylomicronremnants.2.VLDLisdegradedinto3.BothchylomicronremnantandIDLaretakenupbytheliver.4.IDLcanbeconvertedintoLDL,assistedbyApoproteinB-100.5.LDLcantransportcholesteroltotissues.Itcontainsabout2/3oftotalplasmacholesterol.6.HDLreturnsexcesscholesterolfromtissuestotheliverOneaimofcholesterolOneaimofcholesteroltransportationisself-limitationthroughnegativefeedbackLDLtakescholesterolintothecelltosuppressitsownInvolvementofInvolvementofLDLreceptorsincholesteroluptakeandDefectsofLDLreceptorscausecholesteroloverexpressionandthusatherosclerosisLDL:LDL:“bad”ProlongedelevationofLDLlevelsiswhatleadstoBecausetheoxidationofLDLcausesitsaccumulationonthevesselwallandtriggersinflammation,expressionofadhesionmoleculesHDL:“good”HDLcounteractsatherogenesisbytakingexcesscholesterolbacktotheliver.ThingsweknowThingsweknowbutdon’tknowthe1.Dietsrichinsaturatedfattyacidstendtoelevateserumcholesterol2.Aparticularclassofpolyunsaturatedfattyacids,ω-3fattyacids,tendstodepresslevelsofbothserumcholesterolandtriglyceridesandslowthebuild-upofatheroscleroticplaques.ω-3fattyMobilizationofadiposecellMobilizationofadiposecelltriacylglycerolsbyThreelipasesactsequentiallytohydrolyzeTGtoglycerolandTheseenzymesactattheoil–waterinterfaceofthelipidFFAareexportedtothebloodplasma,wheretheyareboundtoalbuminfortransporttoliverandothertissuesforsubsequentoxidation.Glycerolisreleasedtothebloodtobetakenupbylivercells,whereitservesasagluconeogenicsubstrate.ThisisacellThisisjustaThethreelipasesareThethreelipasesareusuallynotonthelipidSomemoleculesonthelipiddroplethavetorecruitthemandthenactivatethem.Perilipin(PL):aproteinthatcoatsthesurfaceoflipiddroplets.CGI-58:sequesteredonthelipiddropletwhenthecellisnotstimulated.Whenthecellisstimulated,itleavesthedroplettorecruitATGL.常WheredoestheinitialsignalWheredoestheinitialsignalcomeStressepinephrine腎上腺素SeetheSeethenextslidefortheactionofControloflipolysisinadiposecellsbyacAMP-mediatedcascadeHormonalactivationofa–adrenergicG-proteincoupledreceptorontheplasmamembraneleadstoelevationofcAMPlevels,whichinturn,activatesproteinkinaseAControloflipolysisinadiposecellsbyacAMP-mediatedcascadeHormonalactivationofa–adrenergicG-proteincoupledreceptorontheplasmamembraneleadstoelevationofcAMPlevels,whichinturn,activatesproteinkinaseA1.PKAphosphorylatesperilipin(PL)and12.CGI-58dissociatesfromphosphorylated-PL,andbindsATGL.33.PhosphorylatedHSLisrecruitedtothelipiddropletandactivatedbyphosphorylated-PL.1247complextothelipiddroplet,activatingthis655.ActivatedATGLhydrolyzesTG,generatesDGand6.HSLhydrolyzesDG,generatesMGand7.MGLcatalyzeMGFFA+NotethatMGLappearstobeacytoplasmiclipase,withouttherequirementofanycofactoronthelipiddroplet.FateoftheFateofthemobilizedFFAsexisttheadipocytebypassivediffusionandfindtheirwaytotheplasma,whereFFAsbecomeboundtoalbumin白蛋白themostabundantplasmaprotein(50%oftotal).Eachalbumincanbindupto10FFAs.FFAsarereleasedfromalbuminandtakenupbytissueslargelybypassivediffusionsothatfattyaciduptakeintocellsisdrivenprimarilybyconcentration.Mostoftheglycerolreleasedtothebloodstreamistakenupbylivercells,Whereitservesasagluconeogenicsubstrate,leadingtoth