chapter 15 part 3 inhibition (1)

8/17/2019 Chapter 15 Part 3 Inhibition (1)

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Chapter 15

Biocatalysis (Part 3)


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Chapter review…

biocatalysisbiocatalysis

Propertiesandmechanisms

of actionsProperties ofenzymes

Mechanismof enzymeaction

Activationenergy Models

Loc

ande

!hypotheses

"nd#ced

$t

Cofactors%ypes &f(') ofcofactors

"nhiition

reversile irreversile

Competitive

oncompetitive

*actors

a+ectingenzymaticreaction

Classi$cation


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LEARNING OUTCOMES

• ,'plain the roles and types ofinhiitors-

•

,'plain inhiition of enzymereaction .

/ reversile inhiition .competitive and

non competitive inhiitor

/ irreversile inhiition . cyanide


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What is an inhibitor

• A s!bstance that interacts "ith theen#y$e to pre%ent it &ro$ "or'in( inthe nor$al $anner) hence stoppin(or slo"in( a speci*c en#y$aticreaction+


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inhiition

reversile

irreversile

Competitive

oncompetitive

! types inhiitors

/ cyanide


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IN,I-ITION

%he rate of enzyme/

controlled reactions may edecreased y the presenceof inhiitors- %here are two

type of inhiitors.• reversile inhiitors

• non reversile inhiitors


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Re%ersible Inhibitors

"nhiitor ind to enzyme y weaonds

%he e+ect of this type of inhiitor istemporary

Ca#ses no permanent damage to theenzyme


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• %he association of the inhiitor

and enzyme is a loose one• "t can easily e removed• 0emoval of the inhiitor restores

the activity of the enzyme to

normal• %here are two types. competitive

inhiitors and non competitiveinhiitors

Re%ersible Inhibitors


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Co$petiti%e

Inhibitors

• "t competes with the s#strate for theactive sites

• %he inhiitor may have similar str#ct#rewith s#strate

•

1hile it remains o#nd to the activesite2 it prevents other s#stratemolec#les from occ#pying that site andso decreases the rate of the reaction

0eversile "nhiitors0eversile "nhiitors


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Co$petiti%e Inhibitors 0eversile "nhiitors0eversile "nhiitors


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%he s#strate contin#es to #se any#na+ected enzyme

#strate and inhiitor are in directcompetition

%he greater concentration of s#strate2 thegreater their chance of $nding the activesites 4 more s#strate molec#les thaninhiitor molec#les are aro#nd to gain entry

to active site

Competitive

"nhiitors



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• "f the concentration of the s#strate isincreased2 less inhiition occ#rs

Competitive

"nhiitors



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CompetitiveCompetitive

"nhiitors"nhiitors



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Inhibitor absent – The substrate

attaches to the active site of the

enzyme in the normal way.

Reaction takes place as normal.

Inhibitor present – The inhibitor

prevents the normal enzyme-

substrate complex being formed.

The reaction rate is reduced.

Succinic acid

Succinic

dehydrogenase

Malonic acid

Succinic dehidrogenase (enzyme)

Succinic acid fumaric acid

Malonic acid (inhibitor)


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AllosteriAllosteric sitec site



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ot attached to the active site #telsewhere on the enzyme molec#le(allosteric site)-

%hey alter the shape of the enzyme /rendering the active site #nreceptive tos#strate 50

Leaving enzyme less e+ective at catalyzing

the conversion of s#strate to prod#ct-

on competitive "nhiitorson competitive "nhiitors 0eversile "nhiitors0eversile "nhiitors


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"nhiitors and s#strate are not"nhiitors and s#strate are notcompeting for the same sitescompeting for the same sites

An increase in s#strate concentrationAn increase in s#strate concentrationwill not therefore red#ce the e+ect of thewill not therefore red#ce the e+ect of the

inhiitor-inhiitor-

Allosteric site Allosteric site 4 speci$c receptor site on4 speci$c receptor site onsome part of the enzyme molec#lesome part of the enzyme molec#leremote from the active site-remote from the active site-



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• ,-g- – i) some poison asored from

environment act y inhiiting enzymes• Pesticides DDT and parathion are

inhibitor of key enzymes in nervoussystem

– ii) Many antiiotic are inhiitor of speci$c

enzyme in acteria• Penicillin block the active site of

enzyme that many bacteria use tomake their cell walls



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A Competitive inhiitormimic the s#stratecompeting for theactive site

A oncompetitive inhiitorind to the enzyme awayfrom the active site2altering the conformationof the enzyme so that itsactive site no longerf#nction

"nhiition 5f enzyme activity


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"nhiitors leave the enzyme"nhiitors leave the enzyme permanentlydamaged

,nzyme #nale to carry o#t its catalyticf#nction

"nhiitor attaches to the enzyme ycovalent onds

"rreversile "nhiitors"rreversile "nhiitors


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• 6eavy metal ions s#ch as merc#ry (6g !7)and silver (Ag 7 ) ca#se dis#lphide ondsto rea8

• %hese onds help to maintain the shapeof the enzyme molec#le

• 5nce roen the enzyme molec#le

sstr#ct#re ecomes irreversily alteredwith the permanent loss of its catalyticproperties-



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,'ample .

inhiition of cytochrome

o'idase comple' y cyanide



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• Cyanide is a poison chemical compo#nd

which can inhiit the normal activity ofcytochrome o'idase .Cytochrome oxidase is oneof a superfamily of proteins which act as the terminal

enzymes of respiratory chains) 4 and enzyme inmitochondria



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• Cyanide ind tightly to the ironatom of the enzyme cytochromec o'idase 4 inactivate the

enzyme #nale to transport e/

• Blocs the passage of electrontransport chain2 %5P the A%P

prod#ction8


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S!$$ary

chapter 15 part 3 inhibition (1)

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