大二上学期文件-生物化学biochemistry糖原代谢

Lecture5GlycogenSynthesisandBreakdownZhangSchoolofLifeScience&: : p390-生物化学下册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(存在于肝细胞和肠细胞光面内质网膜的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(糖基转移酶) utase(磷酸葡萄糖变位酶)5、Glucose6phosphatase(葡萄糖-6-磷酸酶 Tomaintainsufficientlyhighlevelsofglucosethebodyemploystheglucosebiosynthesispathwaycalledgluconeogenesis(糖异生).~180gramsofglucoseneededper(~120gramsforthebrain,~20gramsinbody~190gramsgeneratedperdaybybreakdownofGlycogenGlycogen Glycogen糖原合重糖链长度达到12～18个G时，branchingenzyme（分支酶）将6-7个G残基转到的糖链上，以α-1，6-糖苷键相连。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(胰岛素glucagon(胰高血糖素andepinephrine(肾上腺素)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