Types of Enzyme Inhibitors, Mechanism of Competitive Inhibitors

1. Inhibition Of Enzyme
Action
-Jaiswal
Priyanka
Balister
M.Sc- I

2. Introduction
• Enzyme, a protein molecule, acts as a catalyst in
a reaction.
• Enzyme inhibition- A science of enzyme substrate
reaction influenced by the presence of any organic
chemical, inorganic metal or biosynthetic
compound due to their covalent or non-covalent
interactions with the enzyme active site.
• Enzyme inhibitors- low molecular weight
compounds that bind to an enzyme and decrease
its activity.

3. • Enzyme inhibitors can be specific or non-specific.
• Specific inhibitors can reduce or completely
inhibit the enzyme catalytic activity either
reversibly or irreversibly (permanently).
• Reversible inhibition can be:
- Competitive
- Uncompetitive
- Non-competitive
• Poisons [such as cyanide, carbon monoxide and
polychlorinated biphenols (PCBs)] and drugs are
examples of enzyme inhibitors.

4. Competitive Inhibitors
• A competitive inhibitor is any compound which
closely resembles the chemical structure and
molecular geometry of the substrate.
• The inhibitor competes for the same active site
as the substrate molecule.
• The inhibitor may interact with the enzyme at the
active site, but no reaction takes place.
• Because of the presence of the inhibitor, fewer
active sites are available to act on the substrate.

5. • Since the enzyme's overall structure is unaffected by the
inhibitor, it is still able to catalyze the reaction on
substrate molecules that do bind to an active site.
• Since the inhibitor and substrate bind at the same site,
competitive inhibition can be overcome simply by raising
the substrate concentration.
• Therefore, the amount of enzyme inhibition depends upon
the inhibitor concentration, substrate concentration, and
the relative affinities of the inhibitor and substrate for the
active site.

6. Reaction Scheme
• The reaction scheme that corresponds to competitive
inhibition is:
• The inhibitor reduces the amount of E available for
productive catalysis by the formation of the EI complex.
The inhibitor does not affect the ES complex after it has
formed. The dissociation constant for the inhibitor is KI =
[E][I]/[EI].

7. Michaelis-Menten curve &
Lineweaver Burk Plot
The Lineweaver-Burk plot shows an unchanged Vmax and a
slope that increases with inhibitor concentration.

8. • The Lineweaver-Burk plot shows an unchanged
Vmax and a slope that increases with inhibitor
concentration.
• Steady-state analysis of the effect of the inhibitor
shows that KM is increased by a factor of (1 +
[I]/KI). The resulting form of the Michaelis-
Menten equation is:

9. Disulfiram (Antabuse)
• The drug inhibits the aldehyde oxidase which causes the
accumulation of acetaldehyde with subsequent
unpleasant side-effects of nausea and vomiting.
• This drug is
sometimes used
to help people
overcome the
drinking habit.

10. Ethanol
• Methanol poisoning occurs because the enzyme
alcohol dehydrogenase oxidizes it to formaldehyde,
CH2O, which is a potent poison and formic acid which
attack the optic nerve causing blindness.
• Ethanol is given as an antidote for methanol
poisoning because ethanol is a competitive inhibitor
of methanol to alcohol dehydrogenase.
• Ethanol is oxidized in preference to methanol and
consequently, the oxidation of methanol is slowed
down so that the toxic by-products do not have a
chance to accumulate.

11. References
1. CHEMICAL KINETICS, 3rd
Ed., Keith J. Laidler,
Pearson Publication.
2. BIOCHEMISTRY, 5th
Ed., Richard Harvey &
Denise Ferrier.
3. PHYSICAL CHEMISTRY FOR THE
BIOSCIENCES, Raymond Chang.
4. PRINCIPLES AND TECHNIQUES OF
PRACTICSL BIOCHEMISTRY, 5th
Ed., Keith
Wilson & John Walker.