A patient with confirmed vitamin B12 deficiency has normal serum folate but elevated methylmalonic acid and homocysteine, with megaloblastic marrow despite adequate dietary folate. The 'methyl-folate trap' explains this because:

• A B12 is required for the synthesis of N5,N10-methylene THF from THF
• B Methylmalonyl-CoA mutase consumes methyl-THF as a cofactor
• C Folate absorption in the jejunum requires intrinsic factor
• D The methionine synthase reaction is the only pathway returning methyl-THF to THF ✓

Explanation

Methionine synthase transfers the methyl group of N5-methyl-THF to homocysteine, regenerating both methionine and free THF. This demethylation is the sole route converting methyl-THF back into the THF pool usable for dTMP and purine synthesis. In D12 deficiency, folate accumulates irreversibly as methyl-THF, causing functional folate deficiency with normal serum folate. Methylmalonyl-CoA mutase uses adenosylcobalamin, not methyl-THF, killing option B.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.