Enzyme Inhibitors: An enzyme inhibitor is any substance that can decrease the speed (velocity)
of a reaction catalyzed by an enzyme.
Types of Enzyme Inhibitors:
Reversible and Irreversible.
Reversible inhibitors:
Competitive, Uncompetitive, Non-competitive.
Irreversible inhibitors:
Suicide and Time-dependent.
Competitive inhibitor:
i. They have a structure similar to the substrate and compete directly for the same active
site.
ii. The inhibitory effect can be reversed by increasing the substrate concentration.
iii. Statins (cholesterol), Allopurinol (gout), and Methotrexate (cancer).
Statins:
a. Enzyme Inhibitor: They are known as HMG-CoA reductase inhibitors.
b. Target Enzyme: They target the enzyme HMG-CoA reductase.
c. Therapeutic Action: By inhibiting this enzyme, statins block the synthesis of
cholesterol in the body. This makes them antihyperlipidemic agents, which are
used to reduce illness and mortality in individuals at high risk for cardiovascular
disease.
d. Binding Strength: Statins have a binding affinity for HMG-CoA reductase that is
10,000 times higher than the enzyme's natural substrate, which is why they are so
effective at blocking the process.
Allopurinol:
a. Target Enzyme: The enzyme associated with gout is Xanthine oxidase.
, b. Mechanism of Action: It works by competing with the natural substrate for the
active site of the Xanthine oxidase enzyme.
Uncompetitive Inhibitors:
i. These inhibitors bind to an allosteric site (distinct from the active site) but only to the
enzyme-substrate [ES] complex.
ii. Increasing the substrate concentration actually favors this inhibition.
a. Unlike other inhibitors, an uncompetitive inhibitor only binds to the Enzyme-
Substrate [ES] complex. It cannot bind to the free enzyme (E) on its own.
b. More [ES] Complexes are Formed: High [S] drives the reaction E + S ⇌ ES to
the right, creating a higher concentration of the [ES] complex.
c. More Binding Sites: Since the inhibitor only recognizes and binds to the [ES]
complex, having more of these complexes means there are more available "sites"
for the inhibitor to attach to.
d. Trapping the Complex: Once the inhibitor binds to the [ES] complex, it forms an
ESI complex. This complex is inactive and cannot proceed to create the final
product (P).
iii. Both Vmax and Km are decreased in this type of inhibition.
iv. Example: Phenylalanine inhibiting placental alkaline phosphatase.
Non-competitive inhibitor:
i. They bind to an allosteric site regardless of whether the substrate is present.
ii. The inhibitory effect is constant and not influenced by substrate concentration.
iii. Michaelis-Menten plot and Lineweaver-Burk plot show that non-competitive inhibitors
decrease the Vmax (maximum velocity) of the reaction but do not change the Km (the
affinity of the enzyme for the substrate).
iv. Examples:
a. Heavy metals: Silver (Ag) or mercury (Hg) inhibit enzymes by combining with -
SH (sulfhydryl) groups.
, b. Pepstatin: This is described as a potent inhibitor of pepsin activity. Its clinical
application is to protect patients against reflux tonsil hypertrophy by preventing
pepsin from aggravating the condition.
c. Soybean Trypsin Inhibitor: This is a protease inhibitor that inhibits the enzyme
trypsin. It is sometimes used to prevent cancer growth, specifically Kunitz Soy
Bean Trypsin Inhibitor.
Irreversible Inhibitor:
i. These inhibitors destroy enzyme activity, often by forming permanent bonds with side-
chain groups in the active site.
ii. They cause a permanent loss of the enzyme's catalytic ability.
iii. Suicide inhibitors and Time-dependent inhibitors are specific types of irreversible
inhibitors.
iv. Specific Clinical and Biological Examples:
a. Cyanide
It is an irreversible noncompetitive (binds to allosteric site) inhibitor of
Cytochrome C oxidase, an essential enzyme in cellular respiration.
By blocking this enzyme, it stops the production of ATP and prevents
cells from using oxygen to generate energy.
b. Toxins and Venoms
Inhibitors found in toxins or venoms can irreversibly block vital enzymes
such as acetylcholinesterase.
This blockage can lead to severe physiological consequences, including
paralysis and death.
c. Heavy metal
Metals such as mercury (Hg) and cadmium (Cd) act as irreversible
noncompetitive inhibitors.
They work by blocking a wide range of essential metabolic reactions in
the body.
Clinical Applications of Inhibitors:
of a reaction catalyzed by an enzyme.
Types of Enzyme Inhibitors:
Reversible and Irreversible.
Reversible inhibitors:
Competitive, Uncompetitive, Non-competitive.
Irreversible inhibitors:
Suicide and Time-dependent.
Competitive inhibitor:
i. They have a structure similar to the substrate and compete directly for the same active
site.
ii. The inhibitory effect can be reversed by increasing the substrate concentration.
iii. Statins (cholesterol), Allopurinol (gout), and Methotrexate (cancer).
Statins:
a. Enzyme Inhibitor: They are known as HMG-CoA reductase inhibitors.
b. Target Enzyme: They target the enzyme HMG-CoA reductase.
c. Therapeutic Action: By inhibiting this enzyme, statins block the synthesis of
cholesterol in the body. This makes them antihyperlipidemic agents, which are
used to reduce illness and mortality in individuals at high risk for cardiovascular
disease.
d. Binding Strength: Statins have a binding affinity for HMG-CoA reductase that is
10,000 times higher than the enzyme's natural substrate, which is why they are so
effective at blocking the process.
Allopurinol:
a. Target Enzyme: The enzyme associated with gout is Xanthine oxidase.
, b. Mechanism of Action: It works by competing with the natural substrate for the
active site of the Xanthine oxidase enzyme.
Uncompetitive Inhibitors:
i. These inhibitors bind to an allosteric site (distinct from the active site) but only to the
enzyme-substrate [ES] complex.
ii. Increasing the substrate concentration actually favors this inhibition.
a. Unlike other inhibitors, an uncompetitive inhibitor only binds to the Enzyme-
Substrate [ES] complex. It cannot bind to the free enzyme (E) on its own.
b. More [ES] Complexes are Formed: High [S] drives the reaction E + S ⇌ ES to
the right, creating a higher concentration of the [ES] complex.
c. More Binding Sites: Since the inhibitor only recognizes and binds to the [ES]
complex, having more of these complexes means there are more available "sites"
for the inhibitor to attach to.
d. Trapping the Complex: Once the inhibitor binds to the [ES] complex, it forms an
ESI complex. This complex is inactive and cannot proceed to create the final
product (P).
iii. Both Vmax and Km are decreased in this type of inhibition.
iv. Example: Phenylalanine inhibiting placental alkaline phosphatase.
Non-competitive inhibitor:
i. They bind to an allosteric site regardless of whether the substrate is present.
ii. The inhibitory effect is constant and not influenced by substrate concentration.
iii. Michaelis-Menten plot and Lineweaver-Burk plot show that non-competitive inhibitors
decrease the Vmax (maximum velocity) of the reaction but do not change the Km (the
affinity of the enzyme for the substrate).
iv. Examples:
a. Heavy metals: Silver (Ag) or mercury (Hg) inhibit enzymes by combining with -
SH (sulfhydryl) groups.
, b. Pepstatin: This is described as a potent inhibitor of pepsin activity. Its clinical
application is to protect patients against reflux tonsil hypertrophy by preventing
pepsin from aggravating the condition.
c. Soybean Trypsin Inhibitor: This is a protease inhibitor that inhibits the enzyme
trypsin. It is sometimes used to prevent cancer growth, specifically Kunitz Soy
Bean Trypsin Inhibitor.
Irreversible Inhibitor:
i. These inhibitors destroy enzyme activity, often by forming permanent bonds with side-
chain groups in the active site.
ii. They cause a permanent loss of the enzyme's catalytic ability.
iii. Suicide inhibitors and Time-dependent inhibitors are specific types of irreversible
inhibitors.
iv. Specific Clinical and Biological Examples:
a. Cyanide
It is an irreversible noncompetitive (binds to allosteric site) inhibitor of
Cytochrome C oxidase, an essential enzyme in cellular respiration.
By blocking this enzyme, it stops the production of ATP and prevents
cells from using oxygen to generate energy.
b. Toxins and Venoms
Inhibitors found in toxins or venoms can irreversibly block vital enzymes
such as acetylcholinesterase.
This blockage can lead to severe physiological consequences, including
paralysis and death.
c. Heavy metal
Metals such as mercury (Hg) and cadmium (Cd) act as irreversible
noncompetitive inhibitors.
They work by blocking a wide range of essential metabolic reactions in
the body.
Clinical Applications of Inhibitors:
