Folate is taken up by the cell in forms of folic acid (FA, supplements or fortified foods) or 5-MTHF (natural diet). In the cell, FA is sequentially converted to dihydrofolate (DHF) and then to the active form of the coenzyme, tetrahydrofolate (THF). Both reactions are catalyzed by DHFR (dihydrofolate reductase). Upon accepting a one-carbon group (comes either from serine, glycine, histidine or formate), THF is converted to other forms of folate. For simplicity, only folate coenzymes directly participating in the biosynthesis of nucleotides and methionine are shown (10-FTHF, 10-formyl-THF; CH2-THF, 5,10-methylene-THF). HCY, homocysteine; SAM, S-adenosylmethionine; MS, methionine synthase; TS, thymidylate synthase; MTHFR, methylenetetrahydrofolate reductase. Reaction catalyzed by MS converts 5-MTHF to THF (indicated by dotted arrow) and requires vitamin B12.