Figure 2.
Folate-dependent reactions within cells. Reaction1: 5-methyltetrahydrofolate (5-methylTHF) enters the folate cycle with the provision of its methyl group to homocysteine in the synthesis of methionine, a vitamin B12 dependent reaction mediated by methionine synthase. The tetrahydrofolate (THF) moiety can then acquire a carbon at various oxidation states. Reaction 2: Formate is added at the N10 position to form 10-formylTHF which provides two carbons in Reaction 3 for the synthesis of purines. Reaction 4: 5,10-methyleneTHF is formed from serine and THF in a reaction mediated by serine hydroxyl methyltransferase. Reaction 5: 5-10-methyleneTHF is reduced irreversibly to 5-methylTHF. Reaction 6: 5-formytetrahydrofolate dehydrase is the mechanism by which 5-formylTHF (leucovorin) enters these cyclical folate pathways. Reaction 7: The formation of thymidylate mediated by thymidylate synthase; the THF moiety is oxidized to dihydrofolate (DHF). Reaction 8: DHF is reduced to THF by dihydrofolate reductase. The latter is essential for maintaining THF cofactor pools within mammalian cells.