Folate and cobalamin do not transfer electrons or acyl groups; they transfer one-carbon units. Folate enters the cell and is reduced to tetrahydrofolate (THF), the active coenzyme. THF accepts a single carbon at different oxidation states and carries it between reactions. The most important of these for this chapter is the conversion of deoxyuridylate (dUMP) to thymidylate (dTMP), catalyzed by thymidylate synthase. THF donates the methyl group, and in doing so is oxidized to dihydrofolate (DHF); dihydrofolate reductase (DHFR) regenerates THF so the cycle can continue. Without THF, dTMP cannot be made, and dTMP is the only de novo route to the thymine base of DNA.
Cobalamin works differently. It is a cobalt-containing ring, and it serves as a coenzyme in only two reactions in humans. As methylcobalamin, it accepts a methyl group from 5-methyl-THF and hands it to homocysteine, forming methionine; this is the methionine synthase reaction. As adenosylcobalamin, it assists methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA. The two cobalamin coenzymes are chemically distinct and serve unrelated pathways, which is why cobalamin deficiency has two consequences while folate deficiency has one.