Accepted name: methylenetetrahydrofolate reductase [NAD(P)H]
Reaction: 5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
Other name(s): MTHFR (gene name)
Systematic name: 5-methyltetrahydrofolate:NAD(P)+ oxidoreductase
Comments: A flavoprotein (FAD). The enzyme catalyses the reversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, playing an important role in folate metabolism by regulating the distribution of one-carbon moieties between cellular methylation reactions and nucleic acid synthesis. This enzyme, characterized from Protozoan parasites of the genus Leishmania, is unique among similar characterized eukaryotic enzymes in that it lacks the C-terminal allosteric regulatory domain (allowing it to catalyse a reversible reaction) and uses NADH and NADPH with equal efficiency under physiological conditions. cf. EC, methylenetetrahydrofolate reductase (NADPH); EC, methylenetetrahydrofolate reductase (NADH); and EC, methylenetetrahydrofolate reductase (ferredoxin).
1.  Vickers, T.J., Orsomando, G., de la Garza, R.D., Scott, D.A., Kang, S.O., Hanson, A.D. and Beverley, S.M. Biochemical and genetic analysis of methylenetetrahydrofolate reductase in Leishmania metabolism and virulence. J. Biol. Chem. 281 (2006) 38150–38158. [PMID: 17032644]
[EC created 1978 as EC, transferred 1984 to EC (EC incorporated 2005), modified 2005., modified 2021]