Any substance that can diminish or slow down or

decrease the activity of enzyme is called inhibitor and the process is called inhibition

CONTENTS
1.DEFINATION

2.TYPES OF INHIBITION
a. Reversible Inhibition b. Irreversible Inhibition c. Allosteric Inhibition

2.

I. Define :
In Reversible inhibition the inhibitors bind to the

enzyme through non covalent bonds

 In this the chemical structure of inhibitor closely

resembles that of substrate It binds to the enzyme at the substrate binding site forming an EI complex rather than ES complex

NOTE
NOTE
Km value is increased, but the Vmax remains same.

As the Inhibitor is structurally similar to substrate Due to which they will compete for the same binding site. Affinity of the substrate for the enzyme progressively decreases with increase in concentration of inhibitor

Increase in concentration of substrate will make the inhibitor reversible

1)Xanthine oxidase Allopurinol=gout 2)Folic acid

synthestase methotrexate =cancer 3)HMG CoA

Xanthine

Uric acid
FH4
Mevalonate

purine pyrimidine

HMG CoA
reductase

lovastatin= hypercholestrolemia 4)PABA is essential for bacterial growth . Sulphanamides: bacterial infection 5)Vitamin k is required for blood coagulation Dicumerol: Anticoagulant

 The inhibitor bind at a site other than active site on

the enzyme surface

+S

E S

+S E I E IS

At a slower rate

NOTE Vmax decreases ,but no effect on Km

I.

Define : In Irreversible inhibition the inhibitors bind to the enzyme through covalent bonds.

a) DIFP

OH group serine
Acetyl choline esterase

Ach Acetate + Choline b) Iodoacetate SH group of cystine And imidazole group of histidine

MEAN Allo = other Steros =space The enzyme have a catalytic site as well as extra allosteric site for binding regulatory metabolite which is called as a modulator.

Examples of allosteric inhibition

1.

Carbamyl +

Aspartate carbamylase aspartate ATP(+ve modifier)

carbamyl

aspartate
1.

CTP( -ve modifier)

Hexokinase: activator ADP, Inhibitor :ATP 2. Phosphofrutokinase: activator AMP ,Inhibitor: ATP

Activity of an enzyme is enhanced or sometimes lowered by certain metabolic intermediates (allosteric modifiers) Modifiers binds to the allosteric site and induces conformation changes at the active site ,so that the enzyme activity is accerlated or reduced

Modulator
There are two types of modulator

1)Positive modulator= increases the enzyme activity 2)Negative modulator=inhibit the enzyme activity

 In multienzyme system the first enzyme of the

sequence is the regulatory enzyme. The end product inhibits the enzyme when profused in excess concentration.

Glycine +Succinyl CoA

In multienzyme

system the first enzyme of the squence is the regulatory enzyme.

The end product

ALA Synthase

ALA

-ve modifier

inhibits the enzyme when profuced in excess concentration.

heme

Importance of inhibition
1.) Chemotherapy The most common uses for enzyme inhibitors are as drugs to treat disease. Many of these inhibitors target a human enzyme and aim to correct a pathological condition. However, not all drugs are enzyme inhibitors. Some, such as anti-epileptic drugs, alter enzyme activity by causing more or less of the enzyme to be produced. 2) Metabolic control Enzyme inhibitors are also important in metabolic control. Many metabolic pathways in the cell are inhibited by metabolites that control enzyme activity through allosteric regulation or substrate inhibition.