Methylenetetrahydrofolate Dehydrogenase 1 (MTHFD1)

The MTHFD1 gene encodes a trifunctional protein comprising 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 10-formyltetrahydrofolate synthetase (EC 6.3.4.3). These 3 sequential reactions are involved in the interconversion of 1-carbon derivatives of tetrahydrofolate (THF) which are substrates for methionine, thymidylate, and de novo purine syntheses.

In eukaryotes, the 3 enzymatic activities are properties of a single protein, a homodimer of 100-kD polypeptides. The eukaryotic trifunctional enzyme consists of 2 major domains, an N-terminal containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain in the C terminus.