Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Synonyms
5,10-CH2-H4folate reductase, 5,10-methylenetetrahydrofolate reductase, 5,10-methylenetetrahydrofolate reductase (FADH2), 5,10-methylenetetrahydrofolic acid reductase, 5,10-methylenetetrahydropteroylglutamate reductase, 5-methyltetrahydrofolate:(acceptor) oxidoreductase,
metF, methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase, methylenetetrahydrofolate reductase, methylenetetrahydrofolic acid reductase,
more
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
5,10-methylenetetrahydrofolate + menadiol
5-methyltetrahydrofolate + menadione
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
-
-
-
?
5,10-methylenetetrahydrofolate + reduced methylene blue
5-methyltetrahydrofolate + methylene blue
5-methyltetrahydrofolate + menadione
5,10-methylenetetrahydrofolate + menadiol
5-methyltetrahydrofolate + methylene blue
5,10-methylenetetrahydrofolate + reduced methylene blue
NAD+ + menadiol
NADH + H+ + menadione
reaction of EC 1.6.5.2
-
-
r
NADH + H+ + ferricyanide
NAD+ + ferrocyanide
NADH + H+ + menadione
NAD+ + menadiol
NADH + H+ + methylviologen
NAD+ + reduced methylviologen
additional information
?
-
5,10-methylenetetrahydrofolate + menadiol
5-methyltetrahydrofolate + menadione
-
-
-
r
5,10-methylenetetrahydrofolate + menadiol
5-methyltetrahydrofolate + menadione
-
-
-
r
5,10-methylenetetrahydrofolate + menadiol
5-methyltetrahydrofolate + menadione
-
-
-
r
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
ir
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
ir
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
?
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
?
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
?
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
?
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
?
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
-
-
?
5,10-methylenetetrahydrofolate + reduced methylene blue
5-methyltetrahydrofolate + methylene blue
-
-
-
-
r
5,10-methylenetetrahydrofolate + reduced methylene blue
5-methyltetrahydrofolate + methylene blue
-
-
-
-
r
5-methyltetrahydrofolate + menadione
5,10-methylenetetrahydrofolate + menadiol
-
-
-
r
5-methyltetrahydrofolate + menadione
5,10-methylenetetrahydrofolate + menadiol
-
-
-
?
5-methyltetrahydrofolate + menadione
5,10-methylenetetrahydrofolate + menadiol
-
-
-
r
5-methyltetrahydrofolate + menadione
5,10-methylenetetrahydrofolate + menadiol
-
-
-
r
5-methyltetrahydrofolate + methylene blue
5,10-methylenetetrahydrofolate + reduced methylene blue
-
-
-
-
r
5-methyltetrahydrofolate + methylene blue
5,10-methylenetetrahydrofolate + reduced methylene blue
-
-
-
-
r
NADH + H+ + ferricyanide
NAD+ + ferrocyanide
-
-
-
r
NADH + H+ + ferricyanide
NAD+ + ferrocyanide
-
-
-
r
NADH + H+ + menadione
NAD+ + menadiol
-
-
-
?
NADH + H+ + menadione
NAD+ + menadiol
reaction of EC 1.6.5.2
-
-
r
NADH + H+ + methylviologen
NAD+ + reduced methylviologen
-
-
-
r
NADH + H+ + methylviologen
NAD+ + reduced methylviologen
-
-
-
r
additional information
?
-
no substrate: ferredoxin
-
-
-
additional information
?
-
no substrate: ferredoxin
-
-
-
additional information
?
-
-
the enzyme catalyzes the methylenetetrahydrofolate reduction with methylene blue as an artificial electron donor. The oxidation of methyltetrahydrofolate is mediated with methylene blue as the electron acceptor. Neither NAD+ nor viologen dyes can replace methylene blue in this reaction
-
-
-
additional information
?
-
-
the enzyme catalyzes the methylenetetrahydrofolate reduction with methylene blue as an artificial electron donor. The oxidation of methyltetrahydrofolate is mediated with methylene blue as the electron acceptor. Neither NAD+ nor viologen dyes can replace methylene blue in this reaction
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
0.0004 - 0.287
5,10-methylenetetrahydrofolate
0.075 - 0.106
5-methyltetrahydrofolate
0.0004
5,10-methylenetetrahydrofolate
wild-type, pH 7.2, 4°C
0.0005
5,10-methylenetetrahydrofolate
wild-type, cosubstrate NADH, pH 7.2, 25°C
0.0008
5,10-methylenetetrahydrofolate
pH 7.2, 15°C
0.0039
5,10-methylenetetrahydrofolate
mutant A177V, pH 7.2, 15°C
0.0039
5,10-methylenetetrahydrofolate
wild-type, pH 7.2, 15°C
0.027
5,10-methylenetetrahydrofolate
mutant D120N, cosubstrate NADH, pH 7.2, 25°C
0.0632
5,10-methylenetetrahydrofolate
pH 7.2, 23°C
0.104
5,10-methylenetetrahydrofolate
mutant Q183A, pH 7.2, 4°C
0.106
5,10-methylenetetrahydrofolate
Chimera-1, cosubstrate NADPH, pH 7.2, temperature not specified in the publication
0.108
5,10-methylenetetrahydrofolate
mutant Q183E, pH 7.2, 4°C
0.145
5,10-methylenetetrahydrofolate
pH 7.2, 23°C
0.152
5,10-methylenetetrahydrofolate
Chimera-1, cosubstrate NADH, pH 7.2, temperature not specified in the publication
0.287
5,10-methylenetetrahydrofolate
wild-type, cosubstrate NADH, pH 7.2, temperature not specified in the publication
0.075
5-methyltetrahydrofolate
pH 7.2, 15°C
0.085
5-methyltetrahydrofolate
wild-type, cosubstrate menadione, pH 7.2, 25°C
0.106
5-methyltetrahydrofolate
mutant D120N, cosubstrate menadione, pH 7.2, 25°C
0.0035
NADH
wild-type, pH 7.2, 4°C
0.005
NADH
mutant D120N, pH 7.2, 25°C
0.0066
NADH
mutant Q183E, pH 7.2, 4°C
0.01
NADH
mutant Q183A, pH 7.2, 4°C
0.017
NADH
mutant A177V, pH 7.2, 15°C
0.017
NADH
mutant D120N, cosubstrate menadione, pH 7.2, 25°C
0.017
NADH
wild-type, pH 7.2, 15°C
0.02
NADH
wild-type, pH 7.2, 25°C
0.066
NADH
wild-type, cosubstrate menadione, pH 7.2, 25°C
0.08
NADH
mutant E28Q, cosubstrate menadione, pH 7.2, 25°C
0.24
NADH
presence of 0.05 mM genistein, pH 7.2, 37°C
0.25
NADH
presence of 0.1 mM genistein, pH 7.2, 37°C
0.873
NADH
wild-type, pH 7.2, temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
A177V
mutation mimicks human polymorphism A222V. Mutation does not affect kcat or the Km values but alters FAD binding
D120A
midpoint potential of the mutant increases, the mutant exhibits a 1.2- to 1.5fold faster reduction rate than the wild-type enzyme. Catalytic efficiency (kcat/Km) in the 5-10-methylentetrahydrofolate oxidative half-reaction is significantly decreased
D120K
midpoint potential of the mutant increases, the mutant exhibits a 1.2- to 1.5fold faster reduction rate than the wild-type enzyme. Catalytic efficiency (kcat/Km) in the 5-10-methylentetrahydrofolate oxidative half-reaction is significantly decreased
D120S
midpoint potential of the mutant increases, the mutant exhibits a 1.2- to 1.5fold faster reduction rate than the wild-type enzyme. Catalytic efficiency (kcat/Km) in the 5-10-methylentetrahydrofolate oxidative half-reaction is significantly decreased
D120V
midpoint potential of the mutant increases, the mutant exhibits a 1.2- to 1.5fold faster reduction rate than the wild-type enzyme. Catalytic efficiency (kcat/Km) in the 5-10-methylentetrahydrofolate oxidative half-reaction is significantly decreased
E28Q
mutant is unable to catalyze the reduction of 5,10-methylentetrahydrofolate and is inactive in the physiological oxidoreductase reaction. The mutant is able to bind methyltetrahydrofolate, but reduction of the FAD cofactor is not observed
F223A
mutation impairs NADH and 5,10-methylentetrahydrofolate binding each 40fold yet slows catalysis of both half-reactions less than 2fold
F223L
affinity for 5,10-methylentetrahydrofolate is unaffected by the mutation, the variant catalyzes the oxidative half-reaction 3fold faster than the wild-type enzyme
Q183A
in the reductive half-reaction, NADH binding affinity and the rate of flavin reduction are not hindered by the mutation. Q183A exhibits a 6-10fold lower rate of folate reduction and binds methylentetrahydrofolate with 7-fold lower affinity
Q183E
in the reductive half-reaction, NADH binding affinity and the rate of flavin reduction are not hindered by the mutation and Gln183 plays a minor in the oxidative half-reaction. The mutant displays catalytic constants within 3fold of the wild-type enzyme
additional information
chromosomal copy of MET13 is replaced by an Arabidopsis thaliana MTHFR cDNA (AtMTHFR-1) or by a chimeric sequence (Chimera-1) comprising the yeast N-terminal domain and the AtMTHFR-1 C-terminal domain. Chimera-1 uses both NADH and NADPH and is insensitive to S-adenosyl-L-methionine. Engineered yeast expressing Chimera-1 accumulates 140fold more S-adenosyl-L-methionine and 7fold more methionine than does the wild-type and grows normally. Yeast expressing AtMTHFR-1 accumulates 8fold more S-adenosyl-L-methionine
D120N
midpoint potential of the mutant increases, the mutant exhibits a 1.2- to 1.5fold faster reduction rate than the wild-type enzyme. Catalytic efficiency (kcat/Km) in the 5-10-methylentetrahydrofolate oxidative half-reaction is significantly decreased
D120N
mutant is reduced by NADH 30% more rapidly than the wild-type enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Zuo, C.; Jolly, A.L.; Nikolova, A.P.; Satzer, D.I.; Cao, S.; Sanchez, J.S.; Ballou, D.P.; Trimmer, E.E.
A role for glutamine 183 in the folate oxidative half-reaction of methylenetetrahydrofolate reductase from Escherichia coli
Arch. Biochem. Biophys.
642
63-74
2018
Escherichia coli (P0AEZ1)
brenda
Grabowski, M.; Banecki, B.; Kadzinski, L.; Jakobkiewicz-Banecka, J.; Kazmierkiewicz, R.; Gabig-Ciminska, M.; Wegrzyn, G.; Wegrzyn, A.; Banecka-Majkutewicz, Z.
Genistein inhibits activities of methylenetetrahydrofolate reductase and lactate dehydrogenase, enzymes which use NADH as a substrate
Biochem. Biophys. Res. Commun.
465
363-367
2015
Escherichia coli (P0AEZ1)
brenda
Trimmer, E.E.; Ballou, D.P.; Matthews, R.G.
Methylenetetrahydrofolate reductase from Escherichia coli elucidation of the kinetic mechanism by steady-state and rapid-reaction studies
Biochemistry
40
6205-6215
2001
Escherichia coli (P0AEZ1)
brenda
Trimmer, E.E.; Ballou, D.P.; Ludwig, M.L.; Matthews, R.G.
Folate activation and catalysis in methylenetetrahydrofolate reductase from Escherichia coli roles for aspartate 120 and glutamate 28
Biochemistry
40
6216-6226
2001
Escherichia coli (P0AEZ1)
brenda
Trimmer, E.E.; Ballou, D.P.; Galloway, L.J.; Scannell, S.A.; Brinker, D.R.; Casas, K.R.
Aspartate 120 of Escherichia coli methylenetetrahydrofolate reductase evidence for major roles in folate binding and catalysis and a minor role in flavin reactivity
Biochemistry
44
6809-6822
2005
Escherichia coli (P0AEZ1)
brenda
Lee, M.N.; Takawira, D.; Nikolova, A.P.; Ballou, D.P.; Furtado, V.C.; Phung, N.L.; Still, B.R.; Thorstad, M.K.; Tanner, J.J.; Trimmer, E.E.
Functional role for the conformationally mobile phenylalanine 223 in the reaction of methylenetetrahydrofolate reductase from Escherichia coli
Biochemistry
48
7673-7685
2009
Escherichia coli (P0AEZ1)
brenda
Wohlfarth, G.; Geerligs, G.; Diekert, G.
Purification and properties of a NADH-dependent 5,10-methylenetetrahydrofolate reductase from Peptostreptococcus productus
Eur. J. Biochem.
192
411-417
1990
Blautia producta, Blautia producta Marburg
brenda
Sheppard, C.A.; Trimmer, E.E.; Matthews, R.G.
Purification and properties of NADH-dependent 5, 10-methylenetetrahydrofolate reductase (MetF) from Escherichia coli
J. Bacteriol.
181
718-725
1999
Escherichia coli (P0AEZ1)
brenda
Bertsch, J.; Oeppinger, C.; Hess, V.; Langer, J.; Mueller, V.
Heterotrimeric NADH-oxidizing methylenetetrahydrofolate reductase from the acetogenic bacterium Acetobacterium woodii
J. Bacteriol.
197
1681-1689
2015
Acetobacterium woodii (H6LBX9), Acetobacterium woodii DSM 1030 (H6LBX9)
brenda
Sah, S.; Lahry, K.; Talwar, C.; Singh, S.; Varshney, U.
Monomeric NADH-oxidizing methylenetetrahydrofolate reductases from Mycobacterium smegmatis lack flavin coenzyme
J. Bacteriol.
202
e00709
2020
Mycolicibacterium smegmatis (A0R6M0), Mycolicibacterium smegmatis (A0R6S0), Mycolicibacterium smegmatis ATCC 700084 (A0R6M0), Mycolicibacterium smegmatis ATCC 700084 (A0R6S0)
brenda
Roje, S.; Wang, H.; McNeil, S.D.; Raymond, R.K.; Appling, D.R.; Shachar-Hill, Y.; Bohnert, H.J.; Hanson, A.D.
Isolation, characterization, and functional expression of cDNAs encoding NADH-dependent methylenetetrahydrofolate reductase from higher plants
J. Biol. Chem.
274
36089-36096
1999
Arabidopsis thaliana (O80585), Arabidopsis thaliana (Q9SE60), Zea mays (Q9SE94)
brenda
Roje, S.; Chan, S.Y.; Kaplan, F.; Raymond, R.K.; Horne, D.W.; Appling, D.R.; Hanson, A.D.
Metabolic engineering in yeast demonstrates that S-adenosylmethionine controls flux through the methylenetetrahydrofolate reductase reaction in vivo
J. Biol. Chem.
277
4056-4061
2002
Arabidopsis thaliana (Q9SE60)
brenda
Lu, C.; Liu, Y.; Li, J.; Liu, L.; Du, G.
Engineering of biosynthesis pathway and NADPH supply for improved L-5-methyltetrahydrofolate production by Lactococcus lactis
J. Microbiol. Biotechnol.
31
154-162
2021
Lactococcus lactis subsp. lactis (A0A0B8QP67)
brenda
Guenther, B.; Sheppard, C.; Tran, P.; Rozen, R.; Matthews, R.; Ludwig, M.
The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia
Nat. Struct. Biol.
6
359-365
1999
Escherichia coli (P0AEZ1)
-
brenda