A 60-year-old man with untreated pernicious anemia is evaluated. Serum folate level is reported as high-normal while red cell folate is low. The most likely biochemical explanation is:
- A Increased renal excretion of tetrahydrofolate
- B Trapping of folate as 5-methyl-tetrahydrofolate because methionine synthase is inactive ✓
- C Competitive inhibition of dihydrofolate reductase by accumulated methylmalonic acid
- D Enhanced conversion of folate to N5-formiminotetrahydrofolate
Correct answer: B. Trapping of folate as 5-methyl-tetrahydrofolate because methionine synthase is inactive
Explanation
Methionine synthase uses cobalamin to transfer the methyl group from 5-methyl-THF to homocysteine, regenerating THF. In B12 deficiency this reaction stalls, so folate accumulates as 5-methyl-THF, the only form that cannot be retained intracellularly since it exits the cell. Serum folate therefore rises while red cell and tissue folate fall, the classic methyl-folate trap. MMA accumulation reflects propionyl-CoA carboxylase pathway blockage and does not inhibit DHFR, ruling out option C.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.