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Micronutrient Information Center

De novo thymidylate biosynthesis

Folate coenzymes are essential intermediates in the synthesis of nucleic acid precursors thymidine and purines. Thymidylate biosynthesis pathway involves three enzymes: dihydrofolate reductase, serine hydroxymethyltransferase, and thymidylate synthase. Pyridoxal 5'-phosphate (PLP), a vitamin B6 coenzyme, is required by serine hydroxymethyltransferase, which uses serine as a one-carbon donor for the generation of 5,10-methylenetetrahydrofolate (5,10-methylene THF) from THF. 5,10-methylene THF is then used in both methionine transmethylation cycle (not shown here) and thymidylate biosynthesis. DHF, dihydrofolate; dUMP, deoxyuridine monophosphate; dTMP, deoxythymidine monophosphate (thymidylate); PLP, pyridoxal 5'-phosphate; THF, tetrahydrofolate.