Question

There are many drugs working as inhibitors for certain enzymes, and they have different effects on the targeted enzymes. Generally, some are irreversible inhibitors, this category also includes suicide inhibitors. Some other drugs may work as reversible inhibitors. Please discuss the benefit(s) and disadvantages of using irreversible inhibitor against reversible inhibitors.

Answer 1

Enzyme inhibitors are used as tools for studying enzymes and as drugs for treating certain disorders. Enzyme inhibitors are classified as reversible or irreversible. An irreversible inhibitor forms a stable complex with the enzyme. As a result, the enzyme is permanently inactivated or, at best, is slowly reactivated (requiring hours or days for reversal). Usually, the irreversible inhibitor forms a covalent bond with the enzyme. This typically involves a reaction of the inhibitor with an amino acid residue at the active site of the enzyme. The reaction of aspirin with cyclooxygenase is an example of irreversible enzyme inhibition. Cyclooxygenase catalyzes the first reaction in the biosynthesis of prostaglandins from arachidonate. By acelyating an active site serine (Fig. 2), aspirin causes a stable modification that leads to irreversible inhibition. New cyclooxygenase must be synthesized to regain activity. Aspirin is used as an antiinflammatory, antipyretic, and analgesic agent. It is also used prophylactically to inhibit platelet aggregation and coronary thrombosis.

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