A drug binds the active site of ornithine decarboxylase and undergoes part of the normal catalytic cycle, forming an irreversible covalent adduct that permanently inactivates the enzyme. New enzyme must be synthesized before polyamine synthesis resumes. This drug is used to treat African trypanosomiasis. What type of inhibitor is it?

• A Competitive inhibitor
• B Transition state analog
• C Suicide (mechanism-based) irreversible inhibitor ✓
• D Allosteric inhibitor

Explanation

Eflornithine (difluoromethylornithine) is a classic mechanism-based suicide inhibitor: it is processed by the target enzyme as if it were a substrate, then a reactive intermediate forms a permanent covalent bond that kills the enzyme. A pure competitive inhibitor binds reversibly and its effect can be overcome simply by raising substrate concentration, which does not happen here. Transition state analogs such as allopurinol-related species bind tightly but typically reversibly. Allosteric inhibitors bind outside the active site, which contradicts the stated active site binding.

Reference: Lippincott Illustrated Reviews: Biochemistry, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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