A vegetarian patient presents with megaloblastic anemia and neurological symptoms (subacute combined degeneration). Serum B12 is low; serum folate is normal. The key biochemical link between B12 and folate metabolism that explains why B12 deficiency causes a functional folate trap is:

• A B12 is needed to transport folate across intestinal mucosa
• B B12 (as methylcobalamin) is required by methionine synthase to demethylate methyl-THF, regenerating THF for purine synthesis ✓
• C B12 activates dihydrofolate reductase (DHFR) to maintain the THF pool
• D B12 is needed for folate polyglutamylation inside cells

Explanation

The methyl-folate trap: methyl-THF (N5-methyl-THF, the circulating form of folate) can only be demethylated by methionine synthase (which transfers the methyl group to homocysteine to form methionine) using methylcobalamin (B12) as cofactor. When B12 is deficient, methionine synthase cannot function, N5-methyl-THF accumulates (it cannot be re-oxidized by another route), and the cellular THF pool becomes depleted. This impairs DNA synthesis (dTMP, purines) explaining megaloblastic anemia despite normal or high folate levels in serum.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.