UnitIII Enzymes - PDF document

Unit-III Enzymes Regulation of enzymes Introduction andProperties of Enzymes Enzymes are char

acteristics to facilitate the Enzyme-catalyzed reactions take place Reactants need to pass o

ver the energy barrier, Catalysts reduce the activation energy activation energy. Toxicityof

the biological systemsChemical reactions in living systems are quite different from that in

the industrial Enzyme-catalyzed reactions have the following characteristics in comparison w

ith the general catalyzed reactions:common features: 2 “do” and 2 “don’t&

#148;: no changes in quantity and quality Do not change the unique features: 3 “high

8;Enzyme-catalyzed reactions have very high catalytic efficiencyEnzymes have a high degree of

specificity in response to the external ClassificationOxidoreductasesTransferasesHydrolases

LysasesIsomerasesLigases ConventionalNomenclaturesuffixsubstrates(urease)suffixdescriptiveter

mforreactionstheycatalyze(glutematedehydrogenase)Forhistoric(trypsin,amylase)aftergenes(Rec I

nternationalBiochemistrymaintainsclassificationCategorizeaccordinggeneralorganicreactionscata

lyzednumber,systematicshortercommonenzymeSystematic Nomenclature Unlike conventional catalyst

s, enzymes demonstrate the ability to distinguish different substrates. specificities. su

bstrate and implement their catalytic OC NH2 NH2 + H2O + COurease NH NH2 + H2O methyl urea

Relativespecificity protein kinase Aprotein kinase Cprotein kinase G To phopharylate the -OH

group of serine and threonine in the substrate proteins, leading to the activation of protein

s. Lactate dehydrogenase can recognize only the L-form HC H3C COOH H H3C COOH ABCABC Enzyme-

catalyzed reactions can be regulated in response to the external stimuli, satisfying the need

s of biological processes. Regulations can be accomplished through varying the , adjusting t

he , or changing the substrate concentration. Components of Enzymes Almost all the enzymes

are Some functional groups are Lysozymedifferent parts of the polypeptide chain . Two essen

tial groups + Catalytic groupactive center Active centers consists of only one peptide chainC

onjugated enzymes: holoenzyme = apoenzyme + cofactor(protein)(non-protein)Cofactors: me

tal ions; small organic molecules butloosely bound. Often found in metal-Particularly in the

active center, transfer substrates, stabilize enzyme Small sizeTransferringVitamin-like Tig

htly bind through either Remained Mechanism of Enzyme-Catalyzed Reactions Both E and S are r

igid and fixed, so they must be Induced-fit modelThe binding induces conformational changes

of both E and S, forcing them to get a perfect Induced structural changes Kinetics of Enzyme

-Catalyzed Reactions initial k3k1k2ES E+PE+S = rate constant for ES formation

= rate constant for ES dissociation= rate constant for the product k3k1k2ES E+PE+S The mathe

matical expression of the ��[S] [E], changes of [S] is negligible. Steady-sta

te: the rate of E-S complex disassociation (backward E + S and Describing a hyperboliccurve.

Kmis a characteristic constant of E [S] Km v [S]��[S] Km v Vmax Vmax =VKm+[S

][S] [S]max First order withrespect to [S]Zero order withrespect to [S] one-half of its maxim

umvelocityelocitydetermined by the structure of E, the substrateand environmental conditions

(pH, T, ionic strength, …) 0Vmax V0 max Km The value of affinity of . The larger the th

e smaller the affinity =Kmk1k3k2+ The reaction velocity of an enzymatic Substrate concentrat

ionEnzyme concentrationTemperatureH Inhibitionof Enzyme •Inhibitors are certain molecul

es that can decrease the catalytic rate of an enzyme-catalyzed reaction. •Inhibitors ca

n be normalbody metabolites and foreign (drugs and toxins). Inhibitors The inhibition process

can be either The inhibition can be typebinding targetKmVmaxCompetitiveE only=Noncompetitiv

eE or ES=UncompetitiveES onlySummary of inhibition Metal ionscatalytic power. Cofactors Activ

ator ions(loosely bound)Prosthetic Essential ionsCoenzymes Cofactors Essential ions•Acti

vator ions: loosely and reversibly bound, often participate in the binding of substrates.

49;Metal ions of metalloenzymes: tightly bound, and frequently participate directly Transfer

electronKeep conformation of E-S complex Neutralize anion CosubstratesProsthetic groups The

Their different enzyme-catalyzed reactions. Supply the AA residues. Can be either apoenzy

mes or through many Remained RegulationEnzyme Manybiologicalprocessestakelocationcatalyticca

pacityproductenzymeconcentrationintrinsiccatalyticefficiency.keystepprocessregulateenzymatice

nzymequantity ReasonsforregulationMaintenanceorderedfashionwastingresourcesConservationenergy

consumejustnutrientsadjustmentresponseenvironmentalchanges control more efficient. rate set b

y an enzyme will dictate the whole pathway, namely, the slowest one or the RegulationEnzymeZ

ymogenactivationAllostericregulationCovalentmodification ClinicalApplications Fundamentalenzy

mespresenthaveSynthesizedliverentercirculation.Impairmentlivergeneticdisorderfall enzymestota

llyabsentconcentrationturnoverintracellularenzymesarereleasedintostream.organdamagedmayelevat

eenzymes Isoenzymegroupenzymesthatcatalyzereactiondifferfromstructure,substrateaffinity,maxre

gulatoryproperties.genedifferentiationdifferentgeneproductsdifferentpeptidesgenePresentdiffer

entsystem,subcellularcomponents(e.g)LactatedehydrogenaseCreatine DiagnosticApplicationsUseful

ness:EnzymeassaysprovideimportantinformationconcerningpresenceseverityProvidemonitoringpatien

tresponseapproaches:enzymaticdirectlyagentsmonitorpresencesubstrates Acute pancreatitisLiver

diseases (hepatitis)Heart attack (myocardial infarction)Cancer of prostate glandLactate deh

ydrogenase (LDH)Heart attack, liver diseasesAlcoholismHepatitisMuscular dystrophyEnzymes for

disease diagnosis TherapeuticApplicationsSuccessfultherapeuticSteptokinase:treatingmyocardial

infarction;preventingdamageadministratedimmediatelyafterattackAsparaginase:regressionSeveralr