ENZYMES3:ENZYMEREGULATION

HLeeYuJsuicoJunsay

DepartmentofChemistry

SchoolofScienceandEngineering

AteneodeManilaUniversity1

Inlivingorganisms,Cmingiseverything.TheacCvityofproteins,includingenzymes,oGenmustberegulatedsothattheyfuncConattheproperCmeandplace.

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Howareenzymesregulated?

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ProteinsarethentransportedtodifferentpartsofthecellbymeansofproteintargeEng.

Proteinthatneedtopassthrumembraneshaveanextraaminoacidsequence(calledsignalsequence)totellthecellthattheyneedtobetransported.

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ProteinsalsoneedtobeconCnuouslydegradedforfuncConregulaConandremovalofdamagedormisfoldedproteins.Theprotein’s“kissofdeath”markerisUbiquiHn.

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ProteinsalsoneedtobeconCnuouslydegradedforfuncConregulaConandremovalofdamagedormisfoldedproteins.Theprotein’s“kissofdeath”markerisUbiquiHn.

ALLOSTERICENZYMES

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Aregulatoryenzymecontrolstherateofthewholemetabolicprocess.

RATEmaybeinfluencedby:1.  Finalproduct2.  Substrate3.  Intermediates4.  Someexternalmolecules(likehormones)5.  Oralloftheabove

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Allostericenzymesareregulatoryenzymesthatareregulatedbythereversible,non‐covalentbondingofasignalmolecule(alsocalledeffectormolecule).

Effectormoleculesarelike“stoplights”thatenhance(go!)ordecrease(stop!)enzymeacHvity.

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AllostericenzymesdonotfollowMMkineCcs.Insteadofhyperboliccurves,theygivesigmoidalcurves.

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Allostericenzymesmaybehavedifferentlyinthepresenceofeffectormolecules.

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RegulaConmaybehomotropicorheterotropic.

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AllostericenzymesmaybedescribedusingtheMWCconcertedmodelorsequenCalmodel.

+negaCveeffector

+posiCveeffector

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AllostericenzymesmaybedescribedusingtheMWCconcertedmodelorsequenHalmodel.

ISOZYMESANDZYMOGENS

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EnzymesthatdifferinaminoacidsequencebutcatalyzethesamereacConarecalledisozymes.

Lactatedehydrogenase(LDH)

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Lactatedehydrogenasesubunitsmaybeoftwopossibleforms:MorH.

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TheyaretailormadetomeettheneedsofagivenCssueordevelopmentstage.MayhavedifferentKMandVmax,occursindifferentCssues,anddifferinregulaCon.

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SomeenzymesareiniCallysynthesizedinaninacCveformandrequireafullmodificaConstepbeforebecomingfullyacCve.TheinacCveprecursorsarecalledzymogens.

 Examples DigesCveenzymes Bloodcloing Proinsulininsulin Procollagencollagen Developmentalprocesses Programmedcelldeath(apoptosis)

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DigesCveenzymesareusuallysynthesizedasazymogenbecausetheycanhaveharmfuleffectsinotherpartsofthebody.

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ZymogensareproteolyCcallycleavedtoformacCveenzymes.Thisprocessisirreversible.

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EnzymeacCvity,oncestarted,isamplifiedinacascadingmechanism.

REVERSIBLEREGULATION

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SomeenzymeregulaConstrategiesmaybereversiblecovalenttransformaCons

KINASE

PHOSPHATASE

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SomeenzymeregulaConstrategiesmaybereversiblecovalenttransformaCons

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SomeenzymeregulaConstrategiesmaybereversiblecovalenttransformaCons