A pharmaceutical company is developing an irreversible inhibitor targeting a serine protease involved in blood coagulation. The inhibitor forms a covalent bond with the serine residue in the active site. Enzymatic activity can only be restored by de novo synthesis of the enzyme protein. Which of the following best describes the mechanism by which this class of inhibitors acts?

• A They mimic the transition state of the substrate, blocking the active site reversibly
• B They bind to the allosteric site, causing a conformational change that reduces substrate affinity
• C They chelate the metal cofactor required for catalysis
• D They covalently modify an essential residue in the active site, permanently inactivating the enzyme ✓

Explanation

Irreversible inhibitors form stable covalent bonds with specific amino acid residues in the active site, permanently inactivating the enzyme. Because the bond cannot be broken under physiological conditions, the enzyme is irreversibly modified and activity can only return through new protein synthesis. Classic examples include organophosphates modifying serine in acetylcholinesterase and aspirin acetylating serine in cyclooxygenase.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.