IUBMB Enzyme Nomenclature


Accepted name: methylenetetrahydrofolate reductase [NAD(P)H]

Reaction: 5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+

For diagram of reaction click here and for its place in C1 metabolism, click here

Other name(s): MTHFR; methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate) reductase; 5,10-methylenetetrahydrofolate reductase (NADPH); 5,10-methylenetetrahydrofolic acid reductase; 5,10-CH2-H4folate reductase; methylenetetrahydrofolate reductase (NADPH2); 5-methyltetrahydrofolate:NAD+ oxidoreductase; methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase; 5,10-methylenetetrahydrofolate reductase; methylenetetrahydrofolate reductase; N5,10-methylenetetrahydrofolate reductase; 5,10-methylenetetrahydropteroylglutamate reductase; N5,N10-methylenetetrahydrofolate reductase; methylenetetrahydrofolic acid reductase; 5-methyltetrahydrofolate:(acceptor) oxidoreductase (incorrect); 5,10-methylenetetrahydrofolate reductase (FADH2); MetF; methylenetetrahydrofolate reductase (NADPH); 5-methyltetrahydrofolate:NADP+ oxidoreductase

Systematic name: 5-methyltetrahydrofolate:NAD(P)+ oxidoreductase

Comments: A flavoprotein (FAD). Menadione can also serve as an electron acceptor.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 71822-25-8


1. Daubner, S.C. and Matthews, R.T. Purification and properties of methylenetetrahydrofolate reductase from pig liver. J. Biol. Chem. 257 (1982) 140-145. [PMID: 6975779]

2. Kutzbach, C. and Stokstad, E.L.R. Mammalian methylenetetrahydrofolate reductase. Partial purification, properties, and inhibition by S-adenosylmethionine. Biochim. Biophys. Acta 250 (1971) 459-477. [PMID: 4399897]

3. Sheppard, C.A., Trimmer, E.E. and Matthews, R.G. Purification and properties of NADH-dependent 5,10-methylenetetrahydrofolate reductase (MetF) from Escherichia coli. J. Bacteriol. 181 (1999) 718-725. [PMID: 9922232]

4. Guenther, B.D., Sheppard, C.A., Tran, P., Rozen, R., Matthews, R.G. and Ludwig, M.L. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat. Struct. Biol. 6 (1999) 359-365. [PMID: 10201405]

[EC created 1978 as EC, transferred 1984 to EC (EC incorporated 2005), modified 2005]

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