enzyme3(酶的抑制)

3.3Enzymeinhibition,主讲人黄霄,WHATISI,inhibitor,KeyNotes,EnzymeinhibitionIrreversibleinhibitionReversibleinhibition,Competitiveinhibition,Noncompetitiveinhibition,Uncompetitiveinhibition,Question,2.Comparisonofcompetitiveinhibition,noncompetitiveinhibitionanduncompetitiveinhibitionofthesimilaritiesanddifferences,1.Whatarethemaintypesofenzymeinhibition.,3.3.1Enzymeinhibition,Inhibitor:anymoleculewhichactsdirectlyonanenzymetoloweritscatalyticrateiscalledaninhibitor.Inhibitorsexist:normalbodymetabolites,foreignsubstances,suchasdrugsortoxins.Twomaintypes:irreversibleandreversible.,types,irreversible,reversible,competitive,noncompetitive,Uncompetitive,3.3.2Irreversibleinhibition,Inhibitionwhichbindirreversiblytoanenzymeoftenformacovalentbondtoanaminoacidresidueatorneartheactivesite,andpermanentlyinactivatetheenzyme.Ser:OH;Cys:SH,Organophosphoruspesticide,PAM-I,lewisite,BAL,3.3Reversibleinhibition,CompetitiveinhibitionNoncompetitiveinhibitionUncompetitiveinhibition,1.Competitiveinhibition,competitiveinhibition,Acompetitiveinhibitortypicallyhasclosestructuralsimilaritiestothenormalsubstratefortheenzyme.Thecompetitiveinhibitorbondsreversiblytotheactivesite.Athighsubstrateconcentrations,theeffectofacompetitiveinhibitorcanbeovercome.,competitiveinhibition,sulfadrug,Dihydro-neopterin,synthetase,reductase,MTX,TheeffectofacompetitiveinhibitoronKmandVmax.,1/V0,1/Vmax,-1/Km,competitiveinhibitor,noinhibitor,2.Noncompetitiveinhibition,noncompetitiveinhibition,Anoncompetitiveinhibitorbindsreversiblyatasiteotherthantheactivesiteandcausesachangeintheoverallthree-dimensionalshapeoftheenzymethatleadstoadecreaseincatalyticactivity.Theenzymemaybindtheinhibitor,thesubstrateorboththeinhibitorandsubstratetogether.,Theeffectsofanoncompetitiveinhibitorcannotbeovercomebyincreasingthesubstrateconcertration.,Noncompetitiveinhibitor,Noinhibitor,TheeffectofanoncompetitiveinhibitoronKmandVmax.,Noinhibitor,Noncompetitiveinhibitor,1/V0,1/Vmax,-1/Km,3.Uncompetitiveinhibition,Uncompetitiveinhibitor,Noinhibitor,Noinhibitor,1/S,1/v,1,3,2,Effectsofreversibleinhibitorsonkineticconstants,3.4Regulationofenzymeactivity,FeedbackregulationAllostericenzymesReversiblecovalentmodificationProteolyticactivationRegulationofenzymesynthesisandbreakdown,3.4.1Feedbackregulation,Anenzymeearlyoninthepathwayisinhibitedbyanend-productofthemetabolicpathwayinwhichitisinvolved.,ABCDZ,E1,E2,E3,En,E1inhibitedbyZ,3.4.2Allostericenzymes,Allostericenzymesoftenhavemorethanoneactivesitewhichcooperativelybindsubstratemolecules,suchthatthebindingofsubstrateatoneactivesiteinducesacomformationalchangeintheenzymethatalterstheaffinityoftheotheractivesiteforsubstrate.,Inaddition,allostericenzymesmaybecontrolledbyeffectormoleculesthatbindtoasiteotherthantheactivesiteandchangetherateofenzymeactivity.,allostericeffector,activesite,Allostericsite,10%,Sequentialmodel,Tensestate,Relaxedstate,Concertedmodel,3.4.3Reversiblecovalentmodification,Theactivityofmanyenzymesisalteredbythereversiblemakingandbreakingofacovalentbondbetweentheenzymeandasmallnonproteingroup.,glycogenphosphorylasephosphorylase,Phosphorylation,12ATP,12Pi3,12A,active,Inactive,E1,E2,adenylylation,3.4.4Proteolyticactivation,Someenzymesaresynthesizedaslargerinactiveprecursorscalledproenzymesorzymogens.Theseareactivatedbytheirreversiblehydrolysisofoneormorepeptidebonds.,trypsinogen,trypsin,Activesite,enterokinase,Homework,fillintheblanks1)Enzymeinhibitiontwomaintypes:()().2)At()concentrationstheactionofacompetitiveinhibitorisovercome.3)anoncompetitiveinhibitortheKmremains().2.AnswerthequestionComparisonofcompetitiveinhibition,noncompetitiveinhibitionanduncompetitiveinhibitionofthesimilari