Enzyme inhibition
A regulatory mechanism in biochemistry
Ismail yasin bham.
231008
DEFINITION
Enzyme inhibitors are substances which bring about a
decrease in catalytic activity of the enzyme
Inhibitors may be organic or inorganic in nature
CLASSIFICATIONS
1. Reversible
2. Irreversible
3. Allosteric
REVERSIBLE
Inhibitors binds noncovalently with enzyme and the inhibition can be reversed if the
Inhibitor is removed
i . Competitive
ii . Non-competitive
COMPETITIVE INHIBITION
The inhibitor structurally resembles the substrate
The inhibitor binds at the active site of the enzyme instead of the substrate that
normally would, hence instead of an E-S complex, an E-I complex is formed
This inhibition can be overcome by a higher substrate concentration
No catalysis takes place.
Vmax remains the same, but Km is increased
COMPETITIVE
Examples
Allopurinol is the competitive inhibitor for the enzyme Xanthine oxidase.
Mellonate is a competitive inhibitor for succinate dehydrogenase.
NON COMPETITIVE
The inhibitor binds at a site other than the active site on the enzyme surface.
Inhibitor is not structurally similar to substrate
The enzyme-inhibitor complex can still bind with the substrate , but its efficiency
at transforming substrate to product is decreased
Vmax is lowered and Km is unchanged
NON COMPETITIVE
Examples
Fluoride inhibits glycolytic enzyme enolase
Cyanide inhibits cytochrome oxidase
IRREVERSIBLE
Inhibitors bond covalently with the Enzymes and inactivate them.
Usually toxic or poisonous substances
Once an enzyme is inhibited this way, it remains inactive until new enzyme
molecules are produced
SUICIDE INHIBITION
This is a special type of irreversible inhibition
An inhibitor binds to an enzyme, the inhibitor is then converted to a more potent
form by action of the enzyme, this irreversibly binds the enzyme and inhibitor
The reason this is referred to as suicidial is because the enzyme itself produces
the effective inhibitor which will inactivate said enzyme
EXAMPLE
Allopurinol gets oxidized by xanthine oxidase to form alloxanthine , a more potent
inhibitor of xanthine
The bacterial action of Penicillin is based on suicide inhibition of transpeptidase
Anti inflammatory action of Aspirin is also based on suicide inhibition of
cyclooxygenase by aspirin
ALLOSTERIC INHIBITION
All enzymes have one active site, some have an ‘allosteric’ site in addition to the
active site, where a modifier can bind
This modifier can either enhance or inhibit enzyme activity
Partially reversible
Km is usually increased, Vm in reduced
When inhibitor binds, the configuration of the active site is changed so substrate
cannot bind properly
ALLOSTERIC
EXAMPLE
FEEDBACK INHIBITION
The first step of a process is inhibited by the final product
This is a special type of allosteric inhibition
End product of a metabolic reaction produced in excess inhibits the first enzyme in
the sequence
Prevents build up of intermediates
Example
Production of ATP
Production of cholesterol
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