A patient breathing 50% nitrous oxide for 4 hours is at risk for bone marrow suppression. The mechanism involves irreversible inhibition of which enzyme?
- A Dihydrofolate reductase
- B Thymidylate synthase
- C Methionine synthase ✓
- D Serine hydroxymethyltransferase
Correct answer: C. Methionine synthase
Explanation
Nitrous oxide oxidises the cobalt centre of vitamin B12 (cobalamin) from Co+ to Co3+, irreversibly inactivating methionine synthase. This disrupts methionine and tetrahydrofolate regeneration, impairing DNA synthesis and resulting in megaloblastic bone marrow changes within hours of prolonged exposure. Dihydrofolate reductase is targeted by methotrexate and trimethoprim, not N2O. Thymidylate synthase uses methyleneTHF generated upstream, but the direct enzyme inactivated by N2O is methionine synthase.
Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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