Folate carries one carbon units; B12 transfers the methyl group to homocysteine
Expansion
Folate carries one carbon units for:
- Thymidylate synthesis (dTMP from dUMP), essential for DNA synthesis
- Purine synthesis
- Methionine regeneration
Methionine synthase converts homocysteine to methionine, transferring a methyl group from methyltetrahydrofolate and requiring vitamin B12 as cofactor.
The methyl folate trap: without B12 this reaction stalls, so folate becomes stuck as methyltetrahydrofolate and is unavailable for DNA synthesis. This is why B12 deficiency produces a functional folate deficiency and an identical megaloblastic anaemia.
It also explains the classic clinical trap: giving folate alone in B12 deficiency bypasses the block enough to correct the anaemia while allowing subacute combined degeneration of the cord to progress.
Homocysteine rises in deficiency of B12, folate or B6, and is an independent cardiovascular risk factor. Methylmalonic acid rises in B12 deficiency only, which is why it distinguishes the two.
Methotrexate inhibits dihydrofolate reductase; folinic acid rescue bypasses the block. Trimethoprim does the same to bacterial enzyme selectively.