Reaction: 5-methyltetrahydrofolate + NAD+ = 5,10-methylenetetrahydrofolate + NADH + H+
For diagram of reaction, click here and for its place in C1 metabolism, click here
Other name(s): metF (gene name); 5,10-methylenetetrahydrofolic acid reductase (ambiguous); 5,10-CH2-H4folate reductase (ambiguous); methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase; 5,10-methylenetetrahydrofolate reductase (ambiguous); methylenetetrahydrofolate reductase (ambiguous); N5,10-methylenetetrahydrofolate reductase (ambiguous); 5,10-methylenetetrahydropteroylglutamate reductase (ambiguous); N5,N10-methylenetetrahydrofolate reductase (ambiguous); methylenetetrahydrofolic acid reductase (ambiguous); 5-methyltetrahydrofolate:(acceptor) oxidoreductase (incorrect); 5,10-methylenetetrahydrofolate reductase (FADH2) (ambiguous)
Systematic name: 5-methyltetrahydrofolate:NAD+ oxidoreductase
Comments: A flavoprotein (FAD). The enzyme, found in plants and some bacteria, catalyses the reversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using NADH as the electron donor. It play an important role in folate metabolism by regulating the distribution of one-carbon moieties between cellular methylation reactions and nucleic acid synthesis. These proteins either contain a C-terminal domain that does not mediate allosteric regulation (as in plants) or lack this domain entirely (as in Escherichia coli). As a result, the plant enzymes are not inhibited by S-adenosyl-L-methionine, unlike other eukaryotic enzymes, and catalyse a reversible reaction. cf. EC 1.5.1.53, methylenetetrahydrofolate reductase (NADPH); EC 1.5.1.20, methylenetetrahydrofolate reductase [NAD(P)H]; and EC 1.5.7.1, methylenetetrahydrofolate reductase (ferredoxin).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Wohlfarth, G., Geerligs, G. and Diekert, G. Purification and properties of a NADH-dependent 5,10-methylenetetrahydrofolate reductase from Peptostreptococcus productus. Eur. J. Biochem. 192 (1990) 411-417. [PMID: 2209595]
2. 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]
3. 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]
4. Roje, S., Wang, H., McNeil, S.D., Raymond, R.K., Appling, D.R., Shachar-Hill, Y., Bohnert, H.J. and Hanson, A.D. Isolation, characterization, and functional expression of cDNAs encoding NADH-dependent methylenetetrahydrofolate reductase from higher plants. J. Biol. Chem. 274 (1999) 36089-36096. [PMID: 10593891]
5. Bertsch, J., Oppinger, C., Hess, V., Langer, J.D. and Muller, V. Heterotrimeric NADH-oxidizing methylenetetrahydrofolate reductase from the acetogenic bacterium Acetobacterium woodii. J. Bacteriol. 197 (2015) 1681-1689. [PMID: 25733614]