A 55-year-old dentist required repeated nitrous oxide sedations over six months. He now has fatigue, paresthesias, MCV 116 fL, and hypersegmented neutrophils. Serum B12 assay reads falsely within normal range, but methylmalonic acid is markedly elevated. What is the mechanism?

• A Nitrous oxide competitively inhibits methionine synthase directly
• B Nitrous oxide blocks ileal cubilin receptors preventing B12 uptake
• C Nitrous oxide destroys gastric parietal cells reducing intrinsic factor
• D Nitrous oxide irreversibly oxidizes the cobalt atom of B12, inactivating it functionally ✓

Explanation

Nitrous oxide oxidizes the active cobalt(I) center of cobalamin to an inactive form, functionally depleting B12 despite normal measured levels, which explains the falsely reassuring assay with elevated methylmalonic acid. This is a recognized cause of subacute combined degeneration after prolonged or repeated exposure. It does not affect intrinsic factor production or ileal receptors, and its action on methionine synthase is secondary to cobalamin oxidation rather than direct enzyme competition.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.