Enzymes pdf.pdf of enzymes lippincolt pdf

Enzymes

1. ENZYMES
BIOCHEMISTRY
UNIT-5
ENZYMES

2. CONTENTS
Chemistry
Classification
Mechanismof EnzymeAction
EnzymeKinetics
Inhibition
Activation
Specificity
Chemistry
Classification
Mechanismof EnzymeAction
EnzymeKinetics
Inhibition
Activation
Specificity

3. Introduction
Enzymesarebiologicalcatalyststhatspeed
up the rate of the biochemicalreaction.
Mostenzymes are three dimensionalglobular
proteins(tertiary and quaternarystructure).
Enzymesarebiologicalcatalyststhatspeed
up the rate of the biochemicalreaction.
Mostenzymes are three dimensionalglobular
proteins(tertiary and quaternarystructure).
SomespecialRNAspecies
enzymesandarecalledRibozymes
alsoactas
e.g.
hammerheadribozyme.
Hammerheadenzyme

4. STRUCTURE OFENZYMES
Theactivesiteofanenzymeistheregionthatbinds
substrates,co-factorsandprostheticgroupsandcontains
residuethathelpstoholdthesubstrate.
Activesites generallyoccupy lessthan5% ofthetotalsurface
area ofenzyme.
Activesitehasaspecificshapeduetotertiarystructureof
protein.
Achangeintheshapeofproteinaffectstheshapeofactive
siteandfunctionoftheenzyme.
Theactivesiteofanenzymeistheregionthatbinds
substrates,co-factorsandprostheticgroupsandcontains
residuethathelpstoholdthesubstrate.
Activesites generallyoccupy lessthan5% ofthetotalsurface
area ofenzyme.
Activesitehasaspecificshapeduetotertiarystructureof
protein.
Achangeintheshapeofproteinaffectstheshapeofactive
siteandfunctionoftheenzyme.

5. ACTIVESITE
oActive sitecan be further dividedinto:
ActiveSite
Itchoosesthesubstrate
and bindsit toactivesite.
Itperformsthecatalytic
action ofenzyme.
BindingSite CatalyticSite

6. CO-FACTORS
oCo-factoristhenonproteinmoleculewhichcarriesout
chemicalreactionsthatcannotbeperformedbystandard20
aminoacids.
oCo-factors are of twotypes:
Organicco-factors
Inorganiccofactors
oCo-factoristhenonproteinmoleculewhichcarriesout
chemicalreactionsthatcannotbeperformedbystandard20
aminoacids.
oCo-factors are of twotypes:
Organicco-factors
Inorganiccofactors

7. INORGANICCO-FACTORS
oThese are the inorganic molecules required for theproper
activity ofenzymes.
Examples:
 Enzyme carbonicanhydraserequiresZnforit’sactivity.
 Hexokinase has co-factorMg
ORGANICCO-FACTORS
oThesearetheorganicmoleculesrequiredfortheproper
activityofenzymes.
Example:
 Glycogenphosphorylaserequiresthesmallorganic
molecule pyridoxalphosphate.
++
++
ORGANICCO-FACTORS
oThesearetheorganicmoleculesrequiredfortheproper
activityofenzymes.
Example:
 Glycogenphosphorylaserequiresthesmallorganic
molecule pyridoxalphosphate.

8. TYPESOFORGANICCO-FACTORS
ProstheticGroup Coenzyme
oAprostheticgroupisaoAcoenzymeislooselytightlybound
organicco-boundorganicco-facto
+
r.factore.g.Flavins,heme
E.g.NAD
+
groupsandbiotin.
ProstheticGroup Coenzyme
oAprostheticgroupisaoAcoenzymeislooselytightlybound
organicco-boundorganicco-facto
+
r.factore.g.Flavins,heme
E.g.NAD
+
groupsandbiotin.

9. Anenzymewithit’sco-factorremovedisdesignatedas
apoenzyme.
Thecompletecomplexofaproteinwithallnecessarysmall
organicmolecules,metalionsandothercomponentsis
termedasholoenzymeofholoprotein.
Typesofco-factors Continued…

10. SUBSTRATE
The reactantinbiochemical reactionistermed assubstrate.
When asubstratebindstoan enzymeit formsanenzyme-
substratecomplex.
EnzymeJoinsSubstrate

11. SITES OF ENZYMESYNTHESIS
oEnzymesaresynthesized byribosomeswhich are attachedto
the rough endoplasmicreticulum.
oInformation for the synthesis of enzymeiscarried byDNA.
oAminoacidsarebondedtogethertoformspecificenzyme
accordingtotheDNA’scodes.
oEnzymesaresynthesized byribosomeswhich are attachedto
the rough endoplasmicreticulum.
oInformation for the synthesis of enzymeiscarried byDNA.
oAminoacidsarebondedtogethertoformspecificenzyme
accordingtotheDNA’scodes.

12. INTRACELLULAR AND
EXTRACELLULAR ENZYMES
oIntracellularenzymes aresynthesizedandretainedinthecell
for the use of cellitself.
oTheyare found in the cytoplasm, nucleus,mitochondria and
chloroplast.
Example:
Oxydoreductase catalyses biologicaloxidation.
Enzymes involvedinreductioninthemitochondria.
oIntracellularenzymes aresynthesizedandretainedinthecell
for the use of cellitself.
oTheyare found in the cytoplasm, nucleus,mitochondria and
chloroplast.
Example:
Oxydoreductase catalyses biologicaloxidation.
Enzymes involvedinreductioninthemitochondria.
inthecellbutoExtracellularenzymesaresynthesized
secreted from the celltoworkexternally.
Example:
Digestiveenzymeproducedbythepancreas,arenotusedby
thecellsinthepancreasbutaretransportedtothe
duodenum.

13. CHARACTERISTICS
Enzymesspeedupthereactionbyloweringtheactivation
energy of thereaction.
Theirpresencedoesnoteffectthenature andpropertiesof
endproduct.
Theyarehighlyspecificintheiractionthatiseachenzyme
can catalyze one kind ofsubstrate.
Small amount of enzymes can accelerate chemicalreactions.
EnzymesaresensitivetochangeinpH,temperatureand
substrateconcentration.
Turnovernumberisdefinedasthenumberofsubstrate
moleculestransformedperminutebyoneenzymemolecule.
Catalaseturnovernumber = 6x106/min
Enzymesspeedupthereactionbyloweringtheactivation
energy of thereaction.
Theirpresencedoesnoteffectthenature andpropertiesof
endproduct.
Theyarehighlyspecificintheiractionthatiseachenzyme
can catalyze one kind ofsubstrate.
Small amount of enzymes can accelerate chemicalreactions.
EnzymesaresensitivetochangeinpH,temperatureand
substrateconcentration.
Turnovernumberisdefinedasthenumberofsubstrate
moleculestransformedperminutebyoneenzymemolecule.
Catalaseturnovernumber = 6x106/min

14. NOMENCLATURE OFENZYMES
oAnenzymeisnamedaccording tothenameofthe substrateit
catalyses.
oSomeenzymeswerenamedbeforeasystematicwayof
naming enzyme wasformed.
Example:pepsin, trypsin andrennin
oByaddingsuffix-aseattheendofthenameofthe
substrate, enzymes arenamed.
oEnzyme for catalyzing the hydrolysisistermedashydrolase.
Example:
oAnenzymeisnamedaccording tothenameofthe substrateit
catalyses.
oSomeenzymeswerenamedbeforeasystematicwayof
naming enzyme wasformed.
Example:pepsin, trypsin andrennin
oByaddingsuffix-aseattheendofthenameofthe
substrate, enzymes arenamed.
oEnzyme for catalyzing the hydrolysisistermedashydrolase.
Example:
maltose+water glucose +glucose
maltase

15. EXAMPLES
substrate enzymes products
lactose lactase glucose +galactose
maltose maltase Glucose
cellulose cellulase Glucose
lipid lipase Glycerol +fattyacidlipid lipase Glycerol +fattyacid
starch amylase Maltose
protein protease Peptides +
polypeptide

16. CLASSIFICATION

17. CLASSIFICATIONOFENZYMES
Asystematicclassification ofenzymes hasbeen developedby
InternationalEnzymeCommission.
Thisclassificationisbasedonthetypeofreactionscatalyzed
byenzymes.
There aresixmajorclasses.
Eachclassisfurtherdividedintosubclasses,subsub-classes
andsoon,todescribethehugenumberofdifferentenzyme-
catalyzedreactions.
Asystematicclassification ofenzymes hasbeen developedby
InternationalEnzymeCommission.
Thisclassificationisbasedonthetypeofreactionscatalyzed
byenzymes.
There aresixmajorclasses.
Eachclassisfurtherdividedintosubclasses,subsub-classes
andsoon,todescribethehugenumberofdifferentenzyme-
catalyzedreactions.

18. ENZYMECLASS REACTIONTYPE EXAMPLES
Oxidoreductases Reduction-oxidation
(redox)
Lactate
dehydrogenase
Transferases Move chemical groupHexokinase
Hydrolases Hydrolysis;bond
cleavagewithtransfer
offunctional groupof
water
Lysozyme
Continued……..Classificationofenzymes
Hydrolysis;bond
cleavagewithtransfer
offunctional groupof
water
Lysases Non-hydrolyticbond
cleavage
Fumarase
Isomerases Intramoleculargroup
transfer
(isomerization)
Triosephosphate
isomerase
Ligases Synthesisofnew
covalent bond
betweensubstrates,
usingATPhydrolysis
RNApolymerase

19. MECHANISMOFENZYME
ACTION
MECHANISMOFENZYME
ACTION

20. MECHANISM OF ENZYME ACTION
Thecatalyticefficiencyofenzymesisexplainedbytwo
perspectives:
Thermodynamic
changes
Processes atthe
activesite

21. THERMODYNAMIC CHANGES
All chemicalreactions haveenergybarriersbetweenreactants
andproducts.
Thedifferenceintransitionalstateandsubstrateiscalled
activationalbarrier.

22. THERMODYNAMIC CHANGES
Only a fewsubstances crosstheactivation barrier andchange
intoproducts.
Thatiswhy rate of uncatalyzed reactionsismuchslow.
Enzymesprovideanalternatepathwayforconversionof
substrate intoproducts.
Enzymesacceleratereactionratesbyformingtransitional
state having low activationalenergy.
Hence,thereactionrateisincreasedmanyfoldsinthe
presence ofenzymes.
Thetotalenergyofthesystemremainsthesameand
equilibrium stateisnotdisturbed.
Only a fewsubstances crosstheactivation barrier andchange
intoproducts.
Thatiswhy rate of uncatalyzed reactionsismuchslow.
Enzymesprovideanalternatepathwayforconversionof
substrate intoproducts.
Enzymesacceleratereactionratesbyformingtransitional
state having low activationalenergy.
Hence,thereactionrateisincreasedmanyfoldsinthe
presence ofenzymes.
Thetotalenergyofthesystemremainsthesameand
equilibrium stateisnotdisturbed.

23. LOCK AND KEYMODEL
Proposed byEMILFISCHERin1894.
Lockandkeyhypothesisassumestheactivesiteofan
enzymes are rigidinitsshape.
Thereisnochangeintheactivesitebeforeandaftera
chemicalreaction.

24. INDUCED FITMODEL
Morerecentstudieshaverevealedthattheprocessismuch
morelikelytoinvolveaninducedfitmodel(proposedby
DANIALKOSHLANDin1958).
Accordingtothisexposureofanenzymetosubstratecausea
changeinenzyme,whichcausestheactivesitetochangeit’s
shapetoallowenzymeandsubstratetobind.
Morerecentstudieshaverevealedthattheprocessismuch
morelikelytoinvolveaninducedfitmodel(proposedby
DANIALKOSHLANDin1958).
Accordingtothisexposureofanenzymetosubstratecausea
changeinenzyme,whichcausestheactivesitetochangeit’s
shapetoallowenzymeandsubstratetobind.

25. INDUCEDFITMODEL
26

26. ENZYMESKINETICS

27. INTRODUCTION
“Itisa branchofbiochemistryinwhichwestudythe rateof
enzyme catalyzedreactions.”
Kineticanalysisrevealsthenumberandorderoftheindividual
stepsbywhichenzymestransformsubstrateintoproducts
Studyinganenzyme'skineticsinthiswaycanrevealthe
catalyticmechanismofthatenzyme,itsroleinmetabolism,
howitsactivityiscontrolled,andhowadrugoranagonist
mightinhibittheenzyme
“Itisa branchofbiochemistryinwhichwestudythe rateof
enzyme catalyzedreactions.”
Kineticanalysisrevealsthenumberandorderoftheindividual
stepsbywhichenzymestransformsubstrateintoproducts
Studyinganenzyme'skineticsinthiswaycanrevealthe
catalyticmechanismofthatenzyme,itsroleinmetabolism,
howitsactivityiscontrolled,andhowadrugoranagonist
mightinhibittheenzyme

28. RATESOF REACTIONANDTHEIR
DEPENDENCE ONACTIVATIONENERGY
ActivationEnergy(Ea):
“Theleastamountofenergyneededforachemicalreactionto
takeplace.”
Enzyme(asacatalyst)actsonsubstrateinsuchawaythat
theylowertheactivationenergybychangingtherouteofthe
reaction.
Thereductionofactivationenergy(Ea)increasestheamount
ofreactantmoleculesthatachieveasufficientlevelofenergy,
sothattheyreachtheactivationenergyandformtheproduct.
Example:
Carbonicanhydrasecatalysesthehydrationof10⁶CO₂
moleculespersecondwhichis10⁷xfasterthanspontaneous
hydration.
ActivationEnergy(Ea):
“Theleastamountofenergyneededforachemicalreactionto
takeplace.”
Enzyme(asacatalyst)actsonsubstrateinsuchawaythat
theylowertheactivationenergybychangingtherouteofthe
reaction.
Thereductionofactivationenergy(Ea)increasestheamount
ofreactantmoleculesthatachieveasufficientlevelofenergy,
sothattheyreachtheactivationenergyandformtheproduct.
Example:
Carbonicanhydrasecatalysesthehydrationof10⁶CO₂
moleculespersecondwhichis10⁷xfasterthanspontaneous
hydration.

29. ENZYMESLOWER THEACTIVATIONENERGYOFA
REACTION
Initial energystate
ofsubstrates
Activationenergy
ofuncatalysed
reactionsActivationenergy
of enzymecatalysed
reaction
Energy levels
of
molecules
Final energystateof
products
of enzymecatalysed
reaction
Progress of reaction(time)
Energy levels
of
molecules

30. KINETICSOF ENZYMES CATALYSIS
Enzymescatalysis:
“ Itis anincreasein therateofreactionwith the helpof
enzyme(ascatalyst).”
Catalysisbyenzymesthatproceed
mechanism,typicallyoccurswhen
viauniquereaction
thetransitionstate
Catalysisbyenzymesthatproceed
mechanism,typicallyoccurswhen
viauniquereaction
thetransitionstate
intermediateformsa covalentbondwith theenzyme(covalent
catalysis).
Duringtheprocessofcatalysisenzymesalwaysemerge
unchanged at the completion of thereaction.

31. FACTORSAFFECTINGRATEOF
ENZYMECATALYZEDREACTIONS
Temperature
Hydrogen ionconcentration(pH)
Substrate concentration
Temperature
Hydrogen ionconcentration(pH)
Substrate concentration

32. EFFECT OFTEMPERATURE
Raisingthetemperatureincreasestherateofenzyme
catalyzedreactionbyincreasingkineticenergyofreacting
molecules.
Enzymesworkmaximumoveraparticulartemperatureknown
asoptimumtemperature.Enzymesforhumansgenerally
exhibitstabilitytemperatureupto35-45ᵒC.
ThetemperaturecoefficientisafactorQ₁₀bywhichtherate
ofbiologicalprocessesincreasesfora10ᵒCincreasein
temperature.
FormostbiologicalprocessesQ₁₀=2.
Howeversometimesheatenergycanalsoincreasekinetic
energytoapointthatexceedtheenergybarrierwhichresults
indenaturingofenzymes.
Raisingthetemperatureincreasestherateofenzyme
catalyzedreactionbyincreasingkineticenergyofreacting
molecules.
Enzymesworkmaximumoveraparticulartemperatureknown
asoptimumtemperature.Enzymesforhumansgenerally
exhibitstabilitytemperatureupto35-45ᵒC.
ThetemperaturecoefficientisafactorQ₁₀bywhichtherate
ofbiologicalprocessesincreasesfora10ᵒCincreasein
temperature.
FormostbiologicalprocessesQ₁₀=2.
Howeversometimesheatenergycanalsoincreasekinetic
energytoapointthatexceedtheenergybarrierwhichresults
indenaturingofenzymes.

33. Rate
of
Reaction
Temperature
40
o
C-denatures
5-40
o
C
Increase inActivity
Rate
of
Reaction
0102030405060
<5
o
C-inactive

34. EFFECT OFPH
Rate of almost all enzymescatalyzed reactionsdependson
pH
Mostenzymesexhibit optimal activity at pH value between5
and9
High or lowpHvalue than optimum value will causeionization
of enzyme which resultindenaturation ofenzyme
Rate of almost all enzymescatalyzed reactionsdependson
pH
Mostenzymesexhibit optimal activity at pH value between5
and9
High or lowpHvalue than optimum value will causeionization
of enzyme which resultindenaturation ofenzyme

35. PHAFFECTS THEFORMATIONOF HYDROGEN BONDS
ANDSULPHUR BRIDGES IN PROTEINS ANDSO AFFECTS
SHAPE.
pepsin
trypsin arginase
Rate
of
Reaction
(M)
2 4 8 106
pH
Rate
of
Reaction
(M)
Acidic
Basic

36. MICHAELIS-MENTENMODEL&EFFECTSOF
SUBSTRATECONCENTRATION
Michaelis-MentenModel:
“According to this model theenzymereversibly combineswith
substrate to form an ES complex that subsequentlyyields
product, regeneratingthe freeenzyme.”
E+S ES E+P
k₁
k₋
₁
k
₂





where:
S is thesubstrate
E is theenzyme
ES-isthe enzyme substratecomplex
P is theproduct
K1,K-1and K2 are rateconstants
E+S ES E+P
k₁
k₋
₁
k
₂

37. MICHAELIS-MENTENEQUATION
Michaelis-MentenEquation:
“Itis an equation whichdescribeshowreaction velocityvaries
withsubstrateconcentration.”
V
max[S]
V
o=
K
m+[S]
Where
V
ois the initial reactionvelocity.
V
maxis the maximumvelocity.
K
mis the Michaelis constant =(k₋₁+k₂)/k₁.
[S]is the substrateconcentration.
Michaelis-MentenEquation:
“Itis an equation whichdescribeshowreaction velocityvaries
withsubstrateconcentration.”
V
max[S]
V
o=
K
m+[S]
Where
V
ois the initial reactionvelocity.
V
maxis the maximumvelocity.
K
mis the Michaelis constant =(k₋₁+k₂)/k₁.
[S]is the substrateconcentration.

38. ASSUMPTIONS FORMICHAELIS-MENTEN
EQUATION
Following assumptions are made in derivingtheMichaelis-
Mentenequation:
Relativeconcentrations of E andS.
Steady-Stateassumptions
InitialVelocity

39. SUBSTRATECONCENTRATION

40. SUBSTRATECONCENTRATION

41. PHARMACEUTICAL IMPORTANCE
Enzymesarevirtuallyinvolvedinallphysiologicalprocesses
whichmakesthemthetargetsofchoicefordrugsthatcureor
amelioratehumandisease.
Appliedenzymekineticsrepresentstheprincipaltoolbywhich
scientistidentifyandcharacterizetherapeuticagentsthat
selectivelyinhibittheratesofspecificenzymescatalyzed
processes.
Enzymeskineticsthusplayacriticalroleindrugdiscoveryas
well as elaborating the mode of action ofdrugs.
Enzymesarevirtuallyinvolvedinallphysiologicalprocesses
whichmakesthemthetargetsofchoicefordrugsthatcureor
amelioratehumandisease.
Appliedenzymekineticsrepresentstheprincipaltoolbywhich
scientistidentifyandcharacterizetherapeuticagentsthat
selectivelyinhibittheratesofspecificenzymescatalyzed
processes.
Enzymeskineticsthusplayacriticalroleindrugdiscoveryas
well as elaborating the mode of action ofdrugs.

42. FACTORSAFFECTINGENZYMEACTIVITY

43. TEMPERATURE ANDENZYMEACTION
Enzymes
•aremostactiveatan
optimumtemperature
(usually 37°C in
humans).
•show little activityat
lowtemperatures.
•loseactivity athigh
temperaturesas
denaturation occurs
Enzymes
•aremostactiveatan
optimumtemperature
(usually 37°C in
humans).
•show little activityat
lowtemperatures.
•loseactivity athigh
temperaturesas
denaturation occurs

44. PHANDENZYMEACTION
Enzymes
•aremostactiveat
optimum pH.
•contain R groupsof
amino acids with
proper chargesat
optimum pH.
•loseactivityin low or
high pH astertiary
structure isdisrupted.
Enzymes
•aremostactiveat
optimum pH.
•contain R groupsof
amino acids with
proper chargesat
optimum pH.
•loseactivityin low or
high pH astertiary
structure isdisrupted.

45. SUBSTRATECONCENTRATION
Assubstrate
concentration
increases,
•therateofreaction
increases(at constant
enzyme concentration).
•theenzymeeventually
becomessaturated,
giving maximum
activity.
Assubstrate
concentration
increases,
•therateofreaction
increases(at constant
enzyme concentration).
•theenzymeeventually
becomessaturated,
giving maximum
activity.

46. INHIBITIONINHIBITION

47. INHIBITION
oThepreventionof anenzyme processas aresultof interaction of
inhibitors with theenzyme.
INHIBITORS:
Anysubstancethatcandiminishthevelocityofan
enzyme catalyzed reactioniscalled aninhibitor.
oThepreventionof anenzyme processas aresultof interaction of
inhibitors with theenzyme.
INHIBITORS:
Anysubstancethatcandiminishthevelocityofan
enzyme catalyzed reactioniscalled aninhibitor.

48. TYPES OFINHIBITION
Inhibition
Reversible
Competitive Uncompetitive Mixed
Non-
competitive
Irreversible

49. REVERSIBLEINHIBITION
oIt is an inhibition of enzyme activity in which theinhibiting
molecular entity can associate and dissociate from the
protein‘s bindingsite.
TYPESOFREVERSIBLEINHIBITION
oTherearefourtypes:
Competitiveinhibition.
Uncompetitiveinhibition.
Mixedinhibition.
Non-competitiveinhibition.
oIt is an inhibition of enzyme activity in which theinhibiting
molecular entity can associate and dissociate from the
protein‘s bindingsite.
TYPESOFREVERSIBLEINHIBITION
oTherearefourtypes:
Competitiveinhibition.
Uncompetitiveinhibition.
Mixedinhibition.
Non-competitiveinhibition.

50. COMPETITIVEINHIBITION
Inthistypeofinhibition,theinhibitorscompetewiththe
substratefortheactivesite.FormationofE.Scomplexis
reducedwhileanewE.Icomplexisformed.

51. EXAMPLESOFCOMPETITIVE INHIBITION
StatinDrugAsExampleOfCompetitiveInhibition:
StatindrugssuchaslipitorcompetewithHMG-CoA(substrate)
andinhibittheactivesiteofHMGCoA-REDUCTASE (that
bringaboutthecatalysisofcholesterolsynthesis).
StatinDrugAsExampleOfCompetitiveInhibition:
StatindrugssuchaslipitorcompetewithHMG-CoA(substrate)
andinhibittheactivesiteofHMGCoA-REDUCTASE (that
bringaboutthecatalysisofcholesterolsynthesis).

52. UNCOMPETITIVEINHIBITION
Inthistypeofinhibition,inhibitordoesnotcompetewiththe
substratefortheactivesiteofenzymeinsteaditbindsto
anothersiteknownasallostericsite.

53. EXAMPLES OF UNCOMPETITIVE
INHIBITION
Drugstotreatcasesofpoisoningbymethanolorethylene
glycol act as uncompetitiveinhibitors.
Tetramethylenesulfoxideand3-butylthiolene1-oxideare
uncompetitive inhibitors ofliveralcohaldehydrogenase.
Drugstotreatcasesofpoisoningbymethanolorethylene
glycol act as uncompetitiveinhibitors.
Tetramethylenesulfoxideand3-butylthiolene1-oxideare
uncompetitive inhibitors ofliveralcohaldehydrogenase.

54. MIXEDINHIBITION
oInthistypeofinhibitionbothE.IandE.S.Icomplexesare
formed.
oBoth complexes are catalyticallyinactive.
NONCOMPETITIVE INHIBITION
oIt isa special case ofinhibition.
oInthis inhibitorhas thesameaffinityforeither enzymeEor
theE.Scomplex.
oInthistypeofinhibitionbothE.IandE.S.Icomplexesare
formed.
oBoth complexes are catalyticallyinactive.
NONCOMPETITIVE INHIBITION
oIt isa special case ofinhibition.
oInthis inhibitorhas thesameaffinityforeither enzymeEor
theE.Scomplex.

55. IRREVERSIBLEINHIBITION
Thistypeof inhibition involvesthecovalentattachmentof theinhibitor
totheenzyme.
Thecatalytic activityof enzymeiscompletelylost.
Itcan only be restored only by synthesizingmolecules.

56. EXAMPLESOFIRREVERSIBLE
INHIBITION
Aspirinwhichtargetsandcovalentlymodifiesakeyenzyme
involvedininflammationisanirreversibleinhibitor.
SUICIDE INHIBITION:
Itisanunusualtypeofirreversibleinhibitionwherethe
enzymeconvertstheinhibitorintoareactiveforminitsactive
site.
Aspirinwhichtargetsandcovalentlymodifiesakeyenzyme
involvedininflammationisanirreversibleinhibitor.
SUICIDE INHIBITION:
Itisanunusualtypeofirreversibleinhibitionwherethe
enzymeconvertstheinhibitorintoareactiveforminitsactive
site.

57. ACTIVATIONACTIVATION

58. ACTIVATION
Activationisdefinedastheconversionofaninactiveformof
anenzymetoactiveformwhichprocessesthemetabolic
activity.
TYPES OFACTIVATIONTYPES OFACTIVATION
Activation byco-factors.
Conversion of an enzymeprecursor.

59. ACTIVATIONBY COFACTORS
Manyenzymesareactivatedbyco-factors.
Examples:
DNApolymeraseisaholoenzymethatcatalyzesthe
polymerizationofde-oxyribonucleotideintoaDNAstrand.It
usesMg-ionforcatalyticactivity.
HorseliverdehydrogenaseusesZn-ionforit’sactivation.
Manyenzymesareactivatedbyco-factors.
Examples:
DNApolymeraseisaholoenzymethatcatalyzesthe
polymerizationofde-oxyribonucleotideintoaDNAstrand.It
usesMg-ionforcatalyticactivity.
HorseliverdehydrogenaseusesZn-ionforit’sactivation.

60. DIAGNOSTIC SIGNIFICANCES OF
ENZYMES

61. DIAGNOSTIC SIGNIFICANCES
OFISOENZYMES
IsoEnzyme Presentin Elevatedin
LDH1Heatresistant Myocardium,RBCKidney MI
LDH 2 Heatresistant Myocardium, RBCKidneyKidney disease
and Megaoblastic
Anemia
Kidney disease
and Megaoblastic
Anemia
LDH3 Brain Leukemia andMalignancy
LDH 4 Heatlabile Lung andSpleen Pulmonaryinfarction
LDH5Heatlabilelimitedby
urea
Skeletal muscle,Liver Skeletal muscles&Liver
Diseases