文稿5 properties抑制作用

ChapterChapterPropertiesof5.7ReversibleenzymeInhibitionInhibitionofAnactionthatdecreasestheactivityofenzyme,butdoesnotdenaturethestructureis isacompoundthatbindstoanenzymeandinterfereswithitspreventingESpreventingproductsInactivationInactivationofenzyme:denaturationofenzymeleadsactivitylost.Inhibitionofenzyme酶的抑制:enzymeactivitydecreasesbutstructuredoesnotdenature.Reversibleinhibition可逆抑制作用ReversibleReversibleReversibleinhibitorsbindtotheenzyme,theyinhibitby s,andcanberemovedbydialysisorgelfiltration.EnzymesrecoverCompetitiveStructuresoftheinhibitoraresimilarwiththatofEnzymeactivesitecanbindeithersubstratesorinhibitors,butcannotbindbothatsametime.EIcomplexcannotbreakdowntoproduceEandP.CompetitiveiCompetitivei1KM(1[I])1 M ic1K1[I]M KiNoncompetitiveTheinhibitorsandsubstratebindtothedifferentsiteofESIcomplexcannotbreakdowntoproduceP.NoncompetitiveNoncompetitiveNoncompetitive(1[I]1KM(1[I])1 [S])(1 v icNoncompetitiveinhibition 111(1 UncompetitiveUncompetitiveTheinhibitorscannotbindtoenzyme,onlybindtoESESIcomplexcannotbreakdowntoproduceP.UncompetitiveUncompetitive icv K1KM1 (1[I]Uncompetitiveinhibitionv11(1 MeasurementMeasurementofThemostcommonlyusedmethodisthedouble-reciprocalplot,orlineweaver-Burkplot. [I]Slope1V1KM(1[I])1 SlopeCompetitiveCompetitive-oncompetitiveinhibition [I]Slope1+VSlope1KM(1[I])1 NoncompetitiveNoncompetitive-intercept [I]Vmax 1interceptUncompetitiveUncompetitive-ReversibleThemostcommonlyreversibleinhibitoriscompetitiveinhibitor.UsesUsesofenzymeThepharmaceuticalindustryusesenzymeinhibitionstudiestodesignclinicaluseful5.8IrreversibleIrreversibleIrreversibleIrreversibleinhibitorsformscovalentbondwithenzyme,thusremovingactivemoleculesfromtheenzymepopulation. tionofreversible1irreversible tion tionofreversibleirreversibleIrreversibleOrganicphosphoruscompounds有机磷化合物Organicmercury(Hg),arsenic(As)compounds有机、砷化合物Heavymetal重金属Alkylatingagents烷化剂 化物,COPenicillinOrganicOrganicphosphorusSer-195isoneofthecatalyticresiduesattheactivesiteofAnimportantuseofinhibitorsistheidentificationofaminoacidresiduesattheactivesitebyspecificsubstitutionofthereactivesidechains.AffinitylabelAffinityThestructureofinhibitorissimilarwiththatofsubstrate.Theinhibitorhasaactivegroupwhichcanmodifyakeygroupofenzyme.SuchinhibitorsarereferredtoBromohydroxyacetonAffinitySuicideSuicideSuicideinactivatorisanunusualsubstrateofenzyme,havinganhiddengroup.Duringreaction,thehiddengroupisexposedandactivated,thenreactswithactivesiteofenzymeTheenzymelosesitsactivity Organicmercury(Hg),arsenic(As)EffectoftemperatureenzymaticreactionOptimumRaisingtemperaturemayspeedtherateofenzymaticreaction,andmayalsodenatureenzymegradually.““bellshape”curve“钟型”EffectofpHonreactionrateOptimumpHTheeffectofpHpHaffectdissociationofRgroup,soaffecttheconformationofpHaffectdissociationofsubstrate(thatisrare).“bell“bellshapecurve“钟型”canenhancetheactivityofInorganicSimpleorganicActivesiteofcarboxypeptidase5.95.9AllostericAllostericenzymeundergoconformationchangesinresponsetomodulatorThek iccurveofallostericenzymeissigmoidal.Whenasubunitbindsconformationchange,thenthereactiontakesTRenzymeisinTandtherateofreactionisslow.MostMostallostericenzymes（构酶）aremultisubunitactivesitebindsTheregulatorysiteandactivesitearephysicallydist regionsoftheprotein,usuallyon sandsometimesonseparatesubunits.AllostericAllostericaregenerallysmallmetabolites bindstoallostericenzymereversiblyandnoncovalently.Inhibitor,5.10RegulationenzymeRegulationofRegulationofenzymeRegulationtheamountofenzymeisachievedbycontrollingtherateofitssynthesisanddegradation.Regulationofenzymeactivityisthroughreversiblemodulationoftheactivity.RegulationofenzymeAllostericReversiblecovalentAllostericAllostericlostericmodulatorbindstotheregulatorysiteandcausesaconformationalchangeinenzyme.Theconformationalchangeistransmittedtotheactivesiteoftheenzyme,whichchangesshapetoalteritsactivity.Allostericenzymescontrolthekeystepinametabolicpathway(alwaysthefirststep).TheactivityofitselfistightlyPhosphofructokinase-1fromisatetramerof4identicalEachsubunithasseparatedregulatoryandactivesite.Theenzymehasbothallostericinhibitionandactivation. 酸1,6-P-6-P-RegulatoryAllostericactivator:ActiveProducts:ADPand1,6-P-ShowstheproductsADP,1,6-P-FandtheallostericAllostericAllostericADPisactivator.BindingADPisactivator.BindingADPcausesenzymetobeRstate,andhashighaffinityforsubstrate.PEPisinhibitor.BindingPEPcausesenzymetobeTstate,andhaslowaffinityforsubstrate.Bindingmodulatorsresultsaslightrotationofonedimerrelativetotheother.(conformationalchange)GeneralpropertiesofallostericAllostericmodulatorsdonotresemblethesubstratesorproducts.AllstericmodulatorsnoncovalentlytotheRegulatedenzymesare iccurveis[S]0.5BecauseBecausetheallostericenzymesdorelationship,the[S]atwhichvishalfVmaxcannotrefertoKM. Instead,thesymbol[S]0.5orK0.5isoftenusedtorepresentthe[S]givinghalfVmaxofthe以当反应速度以当反应速度v度Vmax为KM[S]0.5或K0.5表［S］=0.1110%90%Inthesimplestcase,substrateandactivatorInthesimplestcase,substrateandactivatormoleculesbindonlytoenzymeinRstate,andinhibitorsbindonlytoenzymesinTstate.AspartateAspartatetranscarbamylase(ATCase)天冬氨酸转氨甲酰酶isthefirstenzyme