A 58-year-old woman with pernicious anemia develops numbness of the feet, loss of ankle jerks, and impaired vibration and position sense. The neurologic damage is attributed to impaired activity of which enzyme reaction?

• A Thymidylate synthase
• B Delta-ALA synthase
• C Methylmalonyl-CoA mutase
• D Methionine synthase ✓

Explanation

Vitamin D12 as methylcobalamin is the cofactor for methionine synthase, which converts homocysteine to methionine. Methionine is required for S-adenosylmethionine production, the universal methyl donor for myelin maintenance. Deficiency therefore causes subacute combined degeneration of the spinal cord. Methylmalonyl-CoA mutase impairment explains the elevated methylmalonic acid but is linked to the hematologic rather than the neurologic manifestations, making it the tempting distractor. Thymidylate synthase depends on folate, and ALA synthase relates to heme synthesis.

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.