Methylenetetrahydrofolate Dehydrogenase (MTHFD)

Methylenetetrahydrofolate dehydrogenase (MTHFD) is a key enzyme in the folate-dependent one carbon metabolism, which is important for the biosynthesis of several amino acids like glycine, alanine and serine, as well as nucleotide bases, formylated methionine and some pro-vitamins. In some bacteria like E. coli, MTHFD (called FolD in this species) is a dual function enzyme that catalyzes the conversion of 5,10-methylenetetrahydrofolate and NADP⁺ to 5,10-methenyltetrahydrofolate and NADPH (dehydrogenase function), and further converts the first product to 10-formyltetrahdrofolate (cyclohydrolase function). Some microorganisms have a separate enzyme for catalyzing the second cyclohydrolase function (FchA), and some species have an alternative pathway for 10-formyltetrahdrofolate production using formyltetrahydrofolate synthetase (Fhs). In eukaryotes, MTHFD is an important anticancer therapy target.