enzyme

maticreactions,themoleculesatthebeginningoftheprocessare

calledsubstrates,andtheenzymeconvertsthemintodifferentmolecules,calledtheproducts.

Likeallcatalysts,enzymesworkbyloweringtheactivationenergyforareaction,thusdramaticallyincreasingtherateofthe

zymereactionratesareall

catalysts,enzymesarenotconsumedbythereactionstheycatalyze,nordotheyaltertheequilibriumofthereactions.

Structuresandmechanisms(protein)

ionthatcontainsthecatalyticresidues,bindsthe

substrate,scanalsocontainsitesthatbindcofactors,whichare

ndingcanrvetoincreaordecreatheenzyme'sactivity,providingameansforfeedback

regulation.

Mostenzymescanbedenatured—thatis,unfoldedandinactivated—byheatingorchemicaldenaturants,whichdisruptthe

ingontheenzyme,denaturationmaybereversibleorirreversible.

Mechanisms

Enzymescanactinveralways,allofwhichlowerΔG‡:

Loweringtheactivationenergybycreatinganenvironmentinwhichthetransitionstateisstabilized(ingthe

shapeofasubstrate—bybindingthetransition-stateconformationofthesubstrate/productmolecules,theenzymedistorts

theboundsubstrate(s)intotheirtransitionstateform,therebyreducingtheamountofenergyrequiredtocompletethe

transition).

Loweringtheenergyofthetransitionstate,butwithoutdistortingthesubstrate,bycreatinganenvironmentwiththe

oppositechargedistributiontothatofthetransitionstate.

mple,temporarilyreactingwiththesubstratetoformanintermediateES

complex,whichwouldbeimpossibleintheabnceoftheenzyme.

ReducingthereactionentropyceringΔH‡

aloneoverlooksthiffect.

,temperatureincreashelptheenzymefunctionanddeveloptheend

r,ifheatedtoomuch,theenzyme’sshapedeterioratesandonlywhenthetemperaturecomes

backtonormaldoestheenzymeregainitsshape.

Dynamicsandfunction

aldynamicsarethemovementofpartsofthe

enzyme'sstructure,suchasindividualaminoacidresidues,agroupofaminoacids,

movksofproteinresiduesthroughoutan

enzyme'nmotionsarevitaltomanyenzymes,butwhether

smallandfastvibrations,orlargerandslowerconformationalmovementsaremoreimportantdependsonthetypeofreaction

r,althoughthemovementsareimportantinbindingandreleasingsubstratesandproducts,itisnotclearif

proteinmovementshelptoacceleratethechemicalstepsinenzymaticreactions.[43]Thenewinsightsalsohaveimplicationsin

understandingallostericeffectsanddevelopingnewdrugs.

Allostericmodulation

AllosterictransitionofanenzymebetweenRandTstates,stabilidbyanagonist,aninhibitorandasubstrate(theMWCmodel)

Mainarticle:Allostericregulation

Allostericsiteesformweak,noncovalentbonds

withthemolecules,angeinconformationtranslatestotheactivesite,

whichthenaffectsthereactionrateoftheenzyme.[44]Allostericinteractionscanbothinhibitandactivateenzymesandarea

commonwaythatenzymesarecontrolledinthebody.[45]

Cofactorsandcoenzymes

Cofactors

r,othersrequirenon-proteinmoleculescalled

orscanbeeitherinorganic(e.g.,metalionsandiron-sulfurclusters)ororganic

compounds(e.g.,flavinandheme).Organiccofactorscanbeeitherprostheticgroups,whicharetightlyboundtoanenzyme,or

coenzymes,whicharereleadfromtheenzyme'mesincludeNADH,NADPHand

oleculestransferchemicalgroupsbetweenenzymes.

Coenzymes

Coenzymesaresmallorthechemicals

suchasriboflavin,micalgroupscarriedincludethehydrideion(H-)carriedbyNAD

orNADP+,thephosphategroupcarriedbyadenosinetriphosphate,theacetylgroupcarriedbycoenzymeA,formyl,

methenylormethylgroupscarriedbyfolicacid.

Thermodynamics

Asallcatalysts,eny,intheprenceofanenzyme,

thereactionrunsinthesamedirectionasitwouldwithouttheenzyme,r,intheabnceoftheenzyme,

otherpossibleuncatalyzed,"spontaneous"reactionsmightleadtodifferentproducts,becauinthoconditionsthisdifferent

productisformedfaster.

Furthermore,enzymescancoupletwoormorereactions,sothatathermodynamicallyfavorablereactioncanbeudto"drive"a

mple,thehydrolysisofATPisoftenudtodriveotherchemicalreactions.[52]

notaltertheequilibriumitlf,butonlythespeedatwhich

mple,carbonicanhydracatalyzesitsreactionineitherdirectiondependingontheconcentrationofits

reactants.

Nevertheless,iftheequilibriumisgreatlydisplacedinonedirection,thatis,inaveryexergonicreaction,thereactioniffectively

heconditionstheenzymewill,infact,onlycatalyzethereactioninthethermodynamicallyalloweddirection.

Inhibition

Enzymereactionratescanbedecreadbyvarioustypesofenzymeinhibitors.

Competitiveinhibition

Incompetitiveinhibition,theinhibitorandsubstratecompeteforthe

enzyme(i.e.,theycannotbindatthesametime).Oftencompetitive

inhibitorsstronglyrembletherealsubstrateoftheenzyme.

Uncompetitiveinhibition

EIS-complexthusformedisinactive.

Non-competitiveinhibition

Non-competitiveinhibitorscanbindtotheenzymeatthesametimeasthesubstrate,

theEIandEIScomplexesareenzymaticallyinactive.

Usofinhibitors

Sinonexampleofaninhibitorthatisudas

adrugisaspirin,whichinhibitstheCOX-1andCOX-2enzymesthatproducetheinflammationmesngerprostaglandin,thus

r,mple,thepoisoncyanideisan

irreversibleenzymeinhibitorthatcombineswiththecopperandironintheactivesiteoftheenzymecytochromecoxidaand

blockscellularrespiration.

ControlofactivityTherearefivemainwaysthatenzymeactivityiscontrolledinthecell.

production(transcriptionandtranslationofenzymegenes)canbeenhancedordiminishedbyacellinrespon

tochangesinthecell'rmofgeneregulationiscalledenzymeinductionandinhibition(e

enzymeinduction).Forexample,bacteriamaybecomeresistanttoantibioticssuchaspenicillinbecauenzymescalled

beta-lactamasareinducedthathydrolythecrucialbeta-lactamringwithinthepenicillinmolecule.

scanbecompartmentalized,withdifferentmetabolicpathwaysoccurringindifferentcellularcompartments.

Forexample,fattyacidsaresynthesizedbyonetofenzymesinthecytosol,endoplasmicreticulumandtheGolgi

apparatusandudbyadifferenttofenzymesasasourceofenergyinthemitochondrion,throughβ-oxidation.[74]

mple,theendproduct(s)ofametabolicpathwayare

ofteninhibitorsforoneofthefirstenzymesofthepathwaythusregulatingtheamountofendproductmadebythe

egulatorymechanismiscalledanegativefeedbackmechanism,becautheamountoftheend

vefeedbackmechanismcaneffectivelyadjusttherateof

sylpsallocatematerialsandenergy

economically,trolofenzymaticactionhelpstomaintaina

stableinternalenvironmentinlivingorganisms.

nincludephosphorylation,myristoylation

mple,intherespontoinsulin,thephosphorylationofmultipleenzymes,includingglycogen

syntha,helpscontrolthesynthesisordegradationofglycogenandallowsthecelltorespondtochangesinblood

sugar.[75]Anotherexampleofprypsin,a

digestiveprotea,isproducedininactiveformaschymotrypsinogeninthepancreasandtransportedinthisformtothe

opstheenzymefromdigestingthepancreasorothertissuesbeforeitentersthegut.

Thistypeofinactiveprecursortoanenzymeisknownasazymogen.

zymesmaybecomeactivatedwhenlocalizedtoadifferentenvironment(educing(cytoplasm)to

anoxidising(periplasm)environment,highpHtolowpHetc.).Forexample,hemagglutininintheinfluenzavirusis

activatedbyaconformationalchangecaudbytheacidicconditions,theoccurwhenitistakenupinsideitshostcell

andentersthelysosome.[76]