大二上學(xué)期文件-生物化學(xué)biochemistry糖原代謝

Lecture5GlycogenSynthesisandBreakdownZhangSchoolofLifeScience&: : p390-生物化學(xué)下冊(cè)p176-1、2、Glycogen3、Glycogen4、ControlofglycogenKEGG:KyotoEncyclopediaofGenesand

O-聚糖合

多糖合成和代GlucoseisstoredasstarchandglycogenincytosolicgranulesinmuscleandlivercellsofvertebratesGlycogenparticlesinalivercellGlycogenGlycogenPhosphorylase磷酸isadisplacementreactioninwhichphosphateistheattackingspeciesandescovalentlyattachedatthepointofbondbreakage-introductionofaphosphorylgroupe.g.Glycogenphosphatase磷酸（酯）–dephosphorolysis,theremovalofaphosphorylgroupfromaphosphateesterwithwaterastheattackingspecies.e.gFructosebisphosphatase-1（果糖-二磷酸酶-1）convertsfructosebisphosphatetofructose6-phosphateinFructosebisphosphatase-GlycogenPhosphorylase(糖原磷酸化酶糖原磷重重重GlycogenGlycogenDegradation(5):-1,6重重 Toleavethe Glucose6-P+H2O=====→Glucose+Glucose6(存在于肝細(xì)胞和腸細(xì)胞光面內(nèi)質(zhì)網(wǎng)膜的WhywouldaninhibitorofGlycogenPhosphorylasebeasuitabletreatmentfordiabetes?重ahomodimericenzyme,subjecttoallostericcontrol.Ittransitionsbetween“relaxed”(active)&“tense”(inhibited)conformations.Aclassofdrugsdevelopedfortreatingthehyperglycemia(高血糖)ofdiabetes(chloroindole-carboxamides),inhibitliverphosphorylaseallosterically.Theseinhibitorsbindatthedimerinterface,stabilizingtheinactive(tense)conformation.重EnzymesinGlycogen2、Glycosyltransferase(糖基轉(zhuǎn)移酶) utase(磷酸葡萄糖變位酶)5、Glucose6phosphatase(葡萄糖-6-磷酸酶 Tomaintainsufficientlyhighlevelsofglucosethebodyemploystheglucosebiosynthesispathwaycalledgluconeogenesis(糖異生).~180gramsofglucoseneededper(~120gramsforthebrain,~20gramsinbody~190gramsgeneratedperdaybybreakdownofGlycogenGlycogen Glycogen糖原合重糖鏈長(zhǎng)度達(dá)到12～18個(gè)G時(shí)，branchingenzyme（分支酶）將6-7個(gè)G殘基轉(zhuǎn)到的糖鏈上，以α-1，6-糖苷鍵相連。分支的形成增加水溶性 GlycogenSynthesis:HowItA37kDprotein,glycogenin,isboththeprimeronwhichnewchainsarebegun,andtheenzymethatlengthensthem.GlycogeninacquiresglucosebyitsglucosyltransferaseactivityfromUDP-Gluinagrouptransferreaction;glucose covalentlyattachedtoTyr194.Glycogensynthasethenjoinsasatightcomplex,andupto7moreresiduesareaddedfromUDP-Glubyglycogenin.Glycogensynthasethentakesover,extendingthechainasitmovesawayfromglycogenin.Andwithbranchingenzymecompletestheglycogenparticle,eventuallydissociating,butglycogeninstaysrightthere!UDP- AGlycogen About55,000glucoseresidues.21nmdiameter.Mrabout107DaSynthesisanddegradation:different MuscleglycogenisfuelformuscleLiverglycogenismostlyconvertedtoglucoseforbloodstreamtransporttoothertissuesInsulin(胰島素glucagon(胰高血糖素andepinephrine(腎上腺素)regulatemammalianglycogenmetabolism重3.1Roleofinsulininglycogen重Insulinincreasesrateofglucosetransportintomuscle,adiposetissueviaGLUT4transporterRegulationofglucosetransportbyinsulinInsulin-GSK3 Insulinstimulatesglycogensynthesisintheliverviathesecondmessengerphosphatidylinositol3,4,5-trisphosphateInsulinbindingtoitsreceptoractivatesatyrosineproteinkinaseinthereceptor,whichphosphorylatesThephosphotyrosineinIRS-1isthenboundbyphosphatidylinositol3-kinase(PI-3K),whichconvertsphosphatidyl-inositol4,5-bisphosphate(PIP2)inthemembranetophosphatidylinositol3,4,5-trisphosphate(PIP3).Aproteinkinase(PDK-1)thatisactivatedwhenboundtoPIP3activatesasecondproteinkinase(PKB),whichphosphorylatesglycogensynthasekinase3(GSK3)initspseudosubstrateregion,inactivatingitbythemechanisms.TheinactivationofGSK3allowsphosphoproteinphosphatase1(PP1)todephosphorylateglycogensynthase,convertingittoitsactiveform.重Glucoseregulationofinsulinsecretionbypancreaticβ-Whentheblood[glucose]↑,glycolysis↑，intracellular[ATP]ClosingKchannels，depolarizingthemembrane,Ca2+channelsopen,Ca2+flowintothecytosolic[Ca2+]↑triggerinsulinreleaseby3.2(3.2(胰高血糖素(receptorsintheRestoresbloodglucoseinhibitingglycogensynthesisandstimulatingglycogendegradationand3.33.3(receptorsinmanyorgans)Stimulatesthebreakdownofglycogento(whichisconvertedtoG6Pisusedforglycolysisinmuscle(can’treleaseglucose)andglucosereleasetothebloodstreamfromth