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Information on EC 1.5.1.20 - methylenetetrahydrofolate reductase [NAD(P)H]
for references in articles please use BRENDA:EC1.5.1.20
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EC Tree 1 Oxidoreductases
1.5 Acting on the CH-NH group of donors
1.5.1 With NAD+ or NADP+ as acceptor
1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H]
IUBMB 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 1.5.1.53, methylenetetrahydrofolate reductase (NADPH); EC 1.5.1.54, methylenetetrahydrofolate reductase (NADH); and EC 1.5.7.1, methylenetetrahydrofolate reductase (ferredoxin).
The enzyme appears in viruses and cellular organisms
- 1.5.1.20
- nitrite
- homocysteine
- medicine
- paracoccus
-
assimilatory
-
denitrification
- chlorate
- narghi
-
resde
- napc
-
molybdoenzyme
- pantotrophus
-
ammonification
- nutrition
- analysis
showSynonyms
respiratory nitrate reductase, 10-methylenetetrahydrofolate reductase, napab, met13, n5,n10-methylenetetrahydrofolate reductase, n5,10-methylenetetrahydrofolate reductase, methylenetetrahydrofolate reductase (nadph), atmthfr-1, 5,10-methylenetetrahydrofolate reductase (nadph), methylenetetrahydrofolic acid reductase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5,10-CH2-H4folate reductase
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-
-
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5,10-methylenetetrahydrofolate reductase
5,10-methylenetetrahydrofolate reductase (NADPH)
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-
-
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5,10-methylenetetrahydrofolic acid reductase
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-
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5,10-methylenetetrahydropteroylglutamate reductase
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5-methyltetrahydrofolate:NAD oxidoreductase
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-
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5-methyltetrahydrofolate:NAD+ oxidoreductase
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-
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5-methyltetrahydrofolate:NADP+ oxidoreductase
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EC 1.1.1.171
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formerly
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EC 1.1.1.68
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formerly
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EC 1.1.99.15
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formerly
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EC 1.7.99.5
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formerly
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MET13
methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase
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-
-
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methylenetetrahydrofolate reductase
methylenetetrahydrofolate reductase (NADPH)
methylenetetrahydrofolic acid reductase
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-
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MetVF-type methylenetetrahydrofolate reductase
MTHFR
MTHFR2
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-
-
-
N5,10-methylenetetrahydrofolate reductase
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-
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N5,N10-methylenetetrahydrofolate reductase
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-
-
-
NADH:CH2-H4folate oxidoreductase
reductase, methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate)
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-
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reductase, methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide)
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-
-
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type II-MTHFR
5,10-methylenetetrahydrofolate reductase
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-
-
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5,10-methylenetetrahydrofolate reductase
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methylenetetrahydrofolate reductase
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methylenetetrahydrofolate reductase
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654163, 684273, 684274, 684291, 684295, 684298, 684314, 684428, 684441, 684442, 684465, 684738, 684805, 685493, 685860, 685894, 685917, 685988, 685990, 685995, 686128, 686133, 686144, 686149, 686185, 686240, 686310, 686329, 686343, 686497, 686513, 686515, 686540, 686572, 686590, 686592, 686633, 686835, 686994, 687023, 687066, 687152, 687167, 687174, 687359, 687832, 687894, 687946, 687957, 688129, 688140, 688142, 688184, 688476, 688554, 688562, 688565, 688704, 688709, 688710, 688715, 688756, 688778, 689031, 689103, 689111, 689282, 689284, 689298, 689333, 689366, 689729, 689833, 689836, 690042, 690049, 690083, 690112, 690122, 690124, 690181, 690199
methylenetetrahydrofolate reductase (NADPH)
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-
-
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MTHFR
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-
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MTHFR
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654163, 684226, 684273, 684274, 684280, 684291, 684295, 684297, 684298, 684314, 684428, 684441, 684442, 684465, 684469, 684473, 684738, 684805, 685493, 685860, 685862, 685893, 685894, 685895, 685917, 685988, 685990, 685995, 686128, 686133, 686144, 686149, 686158, 686185, 686240, 686310, 686329, 686343, 686497, 686513, 686515, 686517, 686540, 686572, 686589, 686590, 686592, 686633, 686829, 686835, 686994, 687023, 687066, 687152, 687167, 687170, 687174, 687359, 687832, 687894, 687946, 687957, 688057, 688129, 688135, 688140, 688142, 688184, 688476, 688554, 688562, 688565, 688688, 688704, 688709, 688710, 688715, 688756, 688778, 689009, 689031, 689103, 689111, 689166, 689282, 689284, 689298, 689329, 689330, 689333, 689366, 689729, 689833, 689836, 690042, 690049, 690083, 690112, 690122, 690124, 690162, 690181, 690199, 690212, 702155, 724809
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
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5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
mechanism
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5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
mechanism, acceptor is free FAD, stereochemistry
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5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
ping-pong bi-bi mechanism, in which NAD(P)+ release precedes the binding of methylenetetrahydrofolate
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5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
substrate binding and catalyic mechanism involve Asp120, half-reaction mechanisms
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5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
NADH adopts a hairpin conformation and is sandwiched between a conserved phenylalanine, F223, and the isoalloxazine ring of FAD, resulting in a complex competent for hydride transfer. The binding sites of the two substrates overlap. Pinog-pong reaction is facilitated by motions of loops L2, L3, L4
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5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
MTHFR is proposed to use the mechanism of flavin-based electron bifurcation
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
MTHFR is proposed to use the mechanism of flavin-based electron bifurcation
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
folate transformations I
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SYSTEMATIC NAME
IUBMB Comments
5-methyltetrahydrofolate:NAD(P)+ oxidoreductase
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 1.5.1.53, methylenetetrahydrofolate reductase (NADPH); EC 1.5.1.54, methylenetetrahydrofolate reductase (NADH); and EC 1.5.7.1, methylenetetrahydrofolate reductase (ferredoxin).
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CAS REGISTRY NUMBER
COMMENTARY
71822-25-8
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9028-69-7
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
1-pyrroline-5-carboxylate + NADH + H+
L-proline + NAD+
-
Substrates: -
Products: -
Products: -
r
5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate + reduced acceptor
(+)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate + oxidized acceptor
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Substrates: equilibrium lies far in favor of 5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate formation, pentaglutamate form binds to the same enzyme site as monoglutamate form
Products: menadione as acceptor for 5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate formation
Products: menadione as acceptor for 5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate formation
?
5,10-methylenetetrahydrofolate + NAD(P)H
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: NADH is the preferred cofactor of the plant enzyme
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
5-methyltetrahydropteroylmonoglutamate + 5,10-methylenetetrahydropteroylhexaglutamate
5,10-methylenetetrahydropteroylmonoglutamate + 5-methyltetrahydropteroylhexaglutamate
-
Substrates: -
Products: -
Products: -
r
NADH + menadione
NAD+ + reduced menadione
Substrates: -
Products: -
Products: -
?
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
Substrates: -
Products: -
Products: -
r
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
Thermus thermophilus HB8 / ATCC 27634 / DSM 579
Substrates: -
Products: -
Products: -
r
(6R,S)-5,10-methylenetetrahydrofolate + ?
?
-
Substrates: assay at 25°C
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + acceptor
5-methyltetrahydrofolate + reduced acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + acceptor
5-methyltetrahydrofolate + reduced acceptor
-
Substrates: -
Products: -
Products: -
ir
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
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Substrates: enzyme in pathway of synthesis of acetate from CO2 via formate and a series of reactions involving tetrahydrofolate and a corrinoid, FADH2 and reduced ferredoxin may serve as natural reductants for 5,10-methylenetetrahydrofolate
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
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Substrates: biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: first step of conversion of 5,10-methylenetetrahydrofolate to methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + ferredoxin
5-methyltetrahydrofolate + reduced ferredoxin
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + ferredoxin
5-methyltetrahydrofolate + reduced ferredoxin
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: folate-mediated one-carbon metabolism
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: physiological direction is the 5-methyltetrahydrofolate formation by transfer of reducing equivalents from NADH to the enzyme-bound FAD and from reduced FAD to methylenetetrahydrofolate
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: physiological direction: 5-methyltetrahydrofolate formation, inhibition by S-adenosylmethionine functions as a feedback-type metabolic regulation in vivo
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
Substrates: folate-mediated one-carbon metabolism
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NADH + H+
5-methyltetrahydrofolate + NAD+
-
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: physiological NADPH-CH2-H4folate oxidoreductase activity
Products: 5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
Products: 5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: equilibrium far on the side of methyltetrahydrofolate formation
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: specific for (+)-diastereoisomer
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: enzyme encoded by MET13 produces 5-methyltetrahydrofolate used for methylation of homocysteine for methionine biosynthesis in vivo, NADPH is the likely natural reductant
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: enzyme encoded by MET13 produces 5-methyltetrahydrofolate used for methylation of homocysteine for methionine biosynthesis in vivo, NADPH is the likely natural reductant
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: -
Products: -
Products: -
ir
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: ping pong bi bi mechanism
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: ferricyanide, dichlorophenolindophenol and cytochrome c can act as electron acceptors
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: equilibrium far on the side of methyltetrahydrofolate formation
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: ping pong kinetics
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: enzyme catalyzes the reduction of quinoid dihydropterins without a 5-substituent
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: enzyme also catalyzes the NADPH-linked reduction of quinoid dihydrofolate and dihydropterin derivates
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: specific for (+)-diastereoisomer
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: first step in biosynthesis of methyl groups
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: branch point in folate metabolism
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: initial enzyme in pathway leading to synthesis of S-adenosylmethionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: overview: role in incorporation of methyltetrahydrofolate into cellular metabolism
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: strong preference of NADH over NADPH
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: FAD, rubredoxin, benzyl viologen and methylene blue as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced ferredoxin as reduced acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: under anaerobic conditions and in absence of electron acceptors, the equilibrium lies far to the 5-methyltetrahydrofolate formation, inclusion of menadione or oxygen promotes the oxidation of 5-methyltetrahydrofolate
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: prefers NADH as reductant
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADPH as reduced acceptor
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADH as reduced acceptor
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADH as reduced acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: under anaerobic conditions and in absence of electron acceptors, the equilibrium lies far to the 5-methyltetrahydrofolate formation, inclusion of menadione or oxygen promotes the oxidation of 5-methyltetrahydrofolate
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
437719, 437722, 437723, 685862, 685893, 685988, 685995, 686128, 686133, 686144, 686158, 686185, 686240, 686310, 686329, 686497, 686513, 686515, 686517, 686540, 686572, 686592, 686633, 686835, 686994, 687946, 687957, 688057, 688129, 688135, 688140, 688142, 688184, 688554, 688565, 688688, 688704, 688709, 689031, 689103, 689111, 689166, 689282, 689284, 689298, 689329, 689330, 689333, 690042, 690049, 690112, 690124, 690212
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
ir
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADPH as reduced acceptor
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: supply of the folate needed for the metabolism of homocysteine: 5-methyltetrahydrofolate is required for the methylation of homocysteine to methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: homocysteine metabolism
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: homocysteine metabolism
Products: 5-methyltetrahydrofolate is the main form of circulating folate
Products: 5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: physiological direction is the 5-methyltetrahydrofolate formation
Products: 5-methyltetrahydrofolate is the main form of circulating folate
Products: 5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: remethylation of homocysteine to methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: remethylation of homocysteine to methionine
Products: 5-methyltetrahydrofolate is the main form of circulating folate
Products: 5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
ir
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: 5,10-methylene-5,6,7,8-tetrahydropteroylmonoglutamate as substrate
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: equilibrium lies far in favor of 5-methyltetrahydrofolate formation
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADH as reduced acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADH as reduced acceptor
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
Products: product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: equilibrium lies far in favor of 5-methyltetrahydrofolate formation
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADPH as reduced acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: equilibrium lies far in favor of 5-methyltetrahydrofolate formation
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADPH as reduced acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: reduced acceptor is FADH2
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: forward reaction: NADPH as reduced acceptor causes irreversible reduction of the flavin coenzyme FAD
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: reverse reaction: menadione as electron acceptor
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: forward reaction: strong preference of NADH over NADPH
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
-
Substrates: enzyme in pathway of synthesis of acetate from CO2 via formate and a series of reactions involving tetrahydrofolate and a corrinoid, FADH2 and reduced ferredoxin may serve as natural reductants for 5,10-methylenetetrahydrofolate, electron transfer from reduced ferredoxin via iron-sulfur centers via enzyme-bound FAD to 5,10-methylenetetrahydrofolate
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
-
Substrates: physiological important reaction: enzyme catalyzes reduction of 5,10-methylenetetrahydrofolate with reduced ferredoxin
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
-
Substrates: enzyme is part of synthesis pathway of acetate from CO2 via a unique tetrahydrofolate-corrinoid pathway
Products: -
Products: -
?
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH
-
Substrates: -
Products: -
Products: -
r
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH + H+
-
Substrates: -
Products: -
Products: -
r
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH + H+
-
Substrates: -
Products: -
Products: -
r
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
-
Substrates: -
Products: -
Products: -
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
-
Substrates: ping pong kinetics
Products: -
Products: -
?
NADPH + H+ + menadione
NADP+ + menadiol
-
Substrates: ping pong kinetics
Products: -
Products: -
?
nitrate + reduced acceptor
nitrite + acceptor
-
Substrates: the enzyme is responsible for anaerobic growth of Bradyrhizobium japonicum under nitrate-respiring conditions
Products: -
Products: -
?
nitrate + reduced acceptor
nitrite + acceptor
-
Substrates: the enzyme is responsible for anaerobic growth of Bradyrhizobium japonicum under nitrate-respiring conditions
Products: -
Products: -
?
nitrate + reduced benzyl viologen
nitrite + benzyl viologen
-
Substrates: -
Products: -
Products: -
?
nitrate + reduced benzyl viologen
nitrite + benzyl viologen
-
Substrates: -
Products: -
Products: -
?
nitrate + reduced benzyl viologen
nitrite + benzyl viologen
-
Substrates: -
Products: -
Products: -
?
nitrate + reduced methyl viologen
nitrite + methyl viologen
-
Substrates: -
Products: -
Products: -
?
nitrate + reduced methyl viologen
nitrite + methyl viologen
-
Substrates: -
Products: -
Products: -
?
nitrate + reduced methyl viologen
nitrite + methyl viologen
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is responsible for the first step in the denitrification process
Products: -
Products: -
?
additional information
?
-
-
Substrates: no direct activity with pyridine nucleotides
Products: -
Products: -
?
additional information
?
-
-
Substrates: no direct activity with pyridine nucleotides
Products: -
Products: -
?
additional information
?
-
-
Substrates: not as electron donor: reduced rubredoxin
Products: -
Products: -
?
additional information
?
-
Substrates: reduced methyl viologen is used as electron donor and the MVred:methylene-THF oxidoreductase activity is followed during the purification procedure. Analysis of carbon and electron flow during acetogenesis from H2 + CO2 or CO
Products: -
Products: -
-
additional information
?
-
Substrates: reduced methyl viologen is used as electron donor and the MVred:methylene-THF oxidoreductase activity is followed during the purification procedure. Analysis of carbon and electron flow during acetogenesis from H2 + CO2 or CO
Products: -
Products: -
-
additional information
?
-
-
Substrates: no direct activity with pyridine nucleotides
Products: -
Products: -
?
additional information
?
-
-
Substrates: catalytic mechanism, Asp-120 and Glu-28 at the flavin active site are relevant to catalysis, Asp-120: located near the enzyme-bound FAD, role in catalysis of folate reduction and in stabilization of the folate intermediate 5-iminium cation, Glu-28: located near N10 of the folate, general acid catalyst to aid in 5-iminium cation formation
Products: -
Products: -
?
additional information
?
-
-
Substrates: no direct activity with pyridine nucleotides
Products: -
Products: -
?
additional information
?
-
-
Substrates: in patients with defects in the enzyme the homocysteine concentrations are increased, hyperhomocysteinemia elevates the risk for cardiovascular disease
Products: -
Products: -
?
additional information
?
-
-
Substrates: reverse reaction: not NADP+ as acceptor
Products: -
Products: -
?
additional information
?
-
-
Substrates: reverse reaction: menadione and 2,6-dichlorophenolindophenol and NADP+ are not effective as electron acceptor
Products: -
Products: -
?
additional information
?
-
-
Substrates: reverse reaction: menadione and 2,6-dichlorophenolindophenol and NADP+ are not effective as electron acceptor
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH
-
Substrates: -
Products: -
Products: -
r
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
-
Substrates: -
Products: -
Products: -
?
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
Substrates: -
Products: -
Products: -
r
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
Thermus thermophilus HB8 / ATCC 27634 / DSM 579
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: enzyme in pathway of synthesis of acetate from CO2 via formate and a series of reactions involving tetrahydrofolate and a corrinoid, FADH2 and reduced ferredoxin may serve as natural reductants for 5,10-methylenetetrahydrofolate
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
-
Substrates: first step of conversion of 5,10-methylenetetrahydrofolate to methionine
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + ferredoxin
5-methyltetrahydrofolate + reduced ferredoxin
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + ferredoxin
5-methyltetrahydrofolate + reduced ferredoxin
Substrates: -
Products: -
Products: -
r
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: folate-mediated one-carbon metabolism
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5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: -
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5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: physiological direction is the 5-methyltetrahydrofolate formation by transfer of reducing equivalents from NADH to the enzyme-bound FAD and from reduced FAD to methylenetetrahydrofolate
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5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
-
Substrates: physiological direction: 5-methyltetrahydrofolate formation, inhibition by S-adenosylmethionine functions as a feedback-type metabolic regulation in vivo
Products: -
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5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
Substrates: folate-mediated one-carbon metabolism
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r
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: physiological NADPH-CH2-H4folate oxidoreductase activity
Products: 5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
Products: 5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: enzyme encoded by MET13 produces 5-methyltetrahydrofolate used for methylation of homocysteine for methionine biosynthesis in vivo, NADPH is the likely natural reductant
Products: -
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5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
-
Substrates: enzyme encoded by MET13 produces 5-methyltetrahydrofolate used for methylation of homocysteine for methionine biosynthesis in vivo, NADPH is the likely natural reductant
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5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: first step in biosynthesis of methyl groups
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5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: branch point in folate metabolism
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5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: initial enzyme in pathway leading to synthesis of S-adenosylmethionine
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5,10-methylenetetrahydrofolate + NADPH
?
-
Substrates: overview: role in incorporation of methyltetrahydrofolate into cellular metabolism
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5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
Substrates: -
Products: -
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5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
-
Substrates: -
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5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: supply of the folate needed for the metabolism of homocysteine: 5-methyltetrahydrofolate is required for the methylation of homocysteine to methionine
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5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: homocysteine metabolism
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5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: homocysteine metabolism
Products: 5-methyltetrahydrofolate is the main form of circulating folate
Products: 5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: physiological direction is the 5-methyltetrahydrofolate formation
Products: 5-methyltetrahydrofolate is the main form of circulating folate
Products: 5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: remethylation of homocysteine to methionine
Products: -
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5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
-
Substrates: remethylation of homocysteine to methionine
Products: 5-methyltetrahydrofolate is the main form of circulating folate
Products: 5-methyltetrahydrofolate is the main form of circulating folate
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5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
-
Substrates: enzyme in pathway of synthesis of acetate from CO2 via formate and a series of reactions involving tetrahydrofolate and a corrinoid, FADH2 and reduced ferredoxin may serve as natural reductants for 5,10-methylenetetrahydrofolate, electron transfer from reduced ferredoxin via iron-sulfur centers via enzyme-bound FAD to 5,10-methylenetetrahydrofolate
Products: -
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5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
-
Substrates: physiological important reaction: enzyme catalyzes reduction of 5,10-methylenetetrahydrofolate with reduced ferredoxin
Products: -
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5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
-
Substrates: enzyme is part of synthesis pathway of acetate from CO2 via a unique tetrahydrofolate-corrinoid pathway
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nitrate + reduced acceptor
nitrite + acceptor
-
Substrates: the enzyme is responsible for anaerobic growth of Bradyrhizobium japonicum under nitrate-respiring conditions
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nitrate + reduced acceptor
nitrite + acceptor
-
Substrates: the enzyme is responsible for anaerobic growth of Bradyrhizobium japonicum under nitrate-respiring conditions
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additional information
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-
-
Substrates: the enzyme is responsible for the first step in the denitrification process
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additional information
?
-
-
Substrates: in patients with defects in the enzyme the homocysteine concentrations are increased, hyperhomocysteinemia elevates the risk for cardiovascular disease
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
enzyme activity depends on the concentration of its cofactor FAD: maximum activity at 0.05 mM FAD
FAD
-
FAD is essential for electron transfer between NADH and methylenetetrahydrofolate
FAD
-
redox properties of enzyme-bound FAD are influenced by Asp120, which electrostatically stabilizes putative 5-iminium cation intermediate during catalysis
FAD
the enzyme contains one FAD prosthetic group bound per dimer. Km for FAD is 0.005 mM. The enzyme activity of the FAD-replete enzyme is approximately 50% compared to the normal purified enzyme
FADH2
-
flavoprotein, reduced acceptor in forward reaction
FMN
the enzyme contains 1.87 mol FMN per mol dimeric heterodimer. MetF binds the flavin
heme
-
the diheme cytochrome NsapB constitutes the small subunit of the nitrate reductase. The two heme groups have nearly parallel heme planes. van der Waals distances with an iron-to-iron distance of 9.9 A. The two propionate side chaind on both heme groups are hydrogen-bonded to each other. The propionates of one of the heme groups are pulled towards the interior of the molecule due to a salt bridge and a number of hydrogen bonds between the propionates and conserved residues
heme
-
the diheme electron transfer small subunit NapB binds to the large subunit with heme II in close proximity to the [4Fe-4S] cluster of NapA. The plasticity of the complex contributes to an efficient electron transfer in the complex from the heme I of NapB to the molybdenum catalytic site of NapA
NAD+
only active with the chimeric mutant enzyme, not with the wild-type
NADH
only active with the chimeric mutant enzyme, not with the wild-type
NADH
-
dual-cofactor specificity with NADH and NADPH under physiological conditions
NADP+
-
poor cofactor for the recombinant wild-type enzyme, but utilized by the chimeric mutant enzyme with activity equal to the activity with NAD+
NADPH
-
NADPH-dependent reduction of methylenetetrahydrofolate, NADPH irreversibly reduces the enzyme-bound flavin
NADPH
-
poor cofactor for the recombinant wild-type enzyme, but utilized by the chimeric mutant enzyme with activity equal to the activity with NADH
NADPH
-
dual-cofactor specificity with NADH and NADPH under physiological conditions
additional information
-
no direct activity with pyridine nucleotides: NADH, NADPH
-
additional information
-
no direct activity with pyridine nucleotides: NADH, NADPH
-
additional information
-
no direct activity with pyridine nucleotides: NADH, NADPH
-
additional information
wild-type shows no activity with NADH/NAD+
-
additional information
-
wild-type shows no activity with NADH/NAD+
-
additional information
FAD is not required, NADPH is highly preferred before NADH
-
additional information
NADH and NADPH are not used as electron donor, but reduced ferredoxin is. The enzyme possesses two predicted 4Fe-4S-clusters in MetV
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
the enzyme dimer has 14.9 mol iron per mol enzyme, it possesses two 4Fe-4S-clusters
Iron
iron-sulfur centre
-
enzyme contains 15.2 molecules iron and 19.5 molecules acid-labile sulfur as iron-sulfur clusters
Molybdenum
additional information
Iron
-
the diheme electron transfer small subunit NapB binds to the large subunit with heme II in close proximity to the [4Fe-4S] cluster of NapA. The plasticity of the complex contributes to an efficient electron transfer in the complex from the heme I of NapB to the molybdenum catalytic site of NapA
Iron
-
15.2 molecules iron per enzyme molecule, enzyme contains iron-sulfur clusters
Molybdenum
-
enzyme contains molybdenum. When molybdenum concentrations are limiting, molybdenum is involved in the regulation of the expression of the nap genes: the ModA mutant lacks both the 90000 Da protein corresponding to the NapA component of nitrate reductase, and the membrane-bound 25000 Da c-type cytochrome NaC
Molybdenum
-
the diheme electron transfer small subunit NapB binds to the large subunit with heme II in close proximity to the [4Fe-4S] cluster of NapA. The plasticity of the complex contributes to an efficient electron transfer in the complex from the heme I of NapB to the molybdenum catalytic site of NapA
additional information
the enzyme dimer has 16.2 mol acid-labile sulfur per mol enzyme
additional information
-
no evidence for participation of heavy metals ions in catalytic process
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
inhibits at high concentrations
(S)-SKI-72
binds MTHFR via its allosteric domain with nanomolar affinity. Assay of MTHFR activity in the presence of (S)-SKI-72 demonstrates inhibition of purified enzyme with submicromolar potency and endogenous MTHFR from HEK293 cell lysate in the low micromolar range, both of which are lower than AdoMet. Nevertheless, unlike AdoMet, (S)-SKI-72 is unable to completely abolish MTHFR activity, even at very high concentrations
(S)-SKI-73
a (S)-SKI-72 prodrug derivative, in which the 9'-amine moiety is cloaked with the trimethyl-locked quinone butanoate moiety, on intact HEK293 cells. Once (S)-SKI-73 passes inside the cell membrane, it is metabolised into (S)-SKI-72 and 60-N benzylhomosinefungin, which then accumulates inside the cell
-
diethyldicarbonate
-
20 mM NADP+ and 20 mM NAD+ partially protected the enzyme against inactivation whereas 20 mM nicotinamide gives complete protection
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
-
-
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
-
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
p-chloromercuribenzoate
-
60% inhibition of the methylenetetrahydrofolate reductase activity at 0.04 mM, 83% inhibition of the menadione reductase activity at 0.04 mM
dihydrofolate
-
competitive with respect to 5,10-methylenetetrahydrofolate and uncompetitive with respect to NADPH
dihydropteroylpolyglutamate
-
most potent inhibitor is dihydropteroylhexaglutamate
-
S-adenosyl-L-methionine
feed-back regulation of the methyl group biosynthesis pathway in vivo, the chimeric mutant enzyme is insensitive to inhibition by S-adenosyl-L-methionine
S-adenosylmethionine
-
inhibition of the enzyme in crude extracts from fresh liver biopsies, but not after purification from cadaver liver
S-adenosylmethionine
-
strong, reversible allosteric inhibition, prevented by S-adenosylhomocysteine
S-adenosylmethionine
SAM, allosteric inhibition by the reaction product. MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition
S-adenosylmethionine
-
inhibitory effect at a physiological concentration, dependent on incubation temperature, binds to an allosteric regulatory site different from catalytic site, reversed by S-adenosylhomocysteine; in vivo feedback-inhibition
S-adenosylmethionine
-
allosteric inhibition; inhibition partially reversed by S-adenosylhomocysteine
S-adenosylmethionine
-
inhibition partially reversed by S-adenosylhomocysteine
S-adenosylmethionine
-
effect on equilibrium between active and inactive form of enzyme
S-adenosylmethionine
-
inhibits both the reduction of the enzyme-bound flavin by 5-methyltetrahydrofolate and the reoxidation of reduced enzyme by 5,10-methylenetetrahydrofolate
additional information
-
no inhibition by S-adenosyl-L-methionine, which is no feed-back regulator of the methyl group biosynthesis pathway in plants
-
additional information
-
vitamin B12 and methionine can repress enzyme biosynthesis
-
additional information
-
inhibiting MTHFR with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells
-
additional information
the regulatory domain of MTHFR can be targeted by small molecules and presents (S)-SKI-72 as an excellent candidate for development of MTHFR inhibitors, docking study, overview. Phosphorylation of MTHFR, which occurs mainly in the N-terminal serine rich region, further sensitises the protein to this inhibition. Enzyme inhibition may be reversed by the binding of S-adenosylhomocysteine (AdoHcy), the demethylated form of Ado-Met, to the regulatory domain. (S)-SKI-72 exhibits poor membrane permeability
-
additional information
-
not inhibitory: S-adenosyl-L-methionine, no substrate inhibition up to 0.25 mM
-
additional information
-
inhibited by a dominant-negative mutant of inositol-requiring enzyme-1, a reported inhibitor of c-Jun (SP600125) and a dominant-negative derivative of c-Jun N-terminal kinase-1 reduce MTHFR activation
-
additional information
-
residues essential for enzyme activity: arginine, histidine, tryptophan
-
additional information
-
gene contains a putative S-adenosylmethionione binding sequence, that is inhibitory in eukaryotic MTHFR
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
homocysteine
-
treatment of cells results in increase in enzyme mRNA and protein
inositol-requiring enzyme-1
-
the induction of MTHFR was also observed after overexpression of inositol-requiring enzyme-1
-
thapsigargin
-
treatment of cells results in increase in enzyme mRNA and protein
Valproic acid
-
300 mg/kg treatment increases MTHFR promoter activity 2.5fold and MTHFR mRNA and protein 3.7fold
additional information
-
transfection of c-Jun and two activators of c-Jun (LiCl and sodium valproate) increase MTHFR expression, MTHFR mRNA is up-regulated by endoplasmic reticulum stress
-
additional information
-
induction of MTHFR is observed after overexpression of inositol-requiring enzyme IRE1 and is inhibited by a dominant-negative mutant of IRE1. Tranfection of c-Jun and its activators LiCl and sodium valproate increase MTHFR expression, whereas inhibitor of c-Jun SP600125 reduces activation
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Abruptio Placentae
Placenta-mediated pregnancy complications are not associated with fetal or paternal factor V Leiden mutation.
Alzheimer Disease
High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms.
Antiphospholipid Syndrome
[Mutations of genes associated with thromboses in ischemic stroke in patients with primary antiphospholipid syndrome]
Arthritis, Rheumatoid
Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treatment in rheumatoid arthritis.
Atherosclerosis
Expression of the C677T Polymorphism of the 5, 10-Methylenetetrahydrofolate Reductase (MTHFR) Gene in Patients with Carotid Artery Atherosclerosis.
Atherosclerosis
The effects of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction.
Cardiovascular Diseases
High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms.
Cardiovascular Diseases
Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project.
Cerebral Infarction
Association of plasma homocysteine level and N5,N10-methylenetetrahydrofolate reductase gene polymorphism with cerebral infarction.
Cerebrovascular Disorders
[Mutations of genes associated with thromboses in ischemic stroke in patients with primary antiphospholipid syndrome]
Congenital Abnormalities
The effects of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction.
Coronary Artery Disease
Genetic polymorphism of MTHFR C677T and premature coronary artery disease susceptibility: A meta-analysis.
Coronary Artery Disease
The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease.
Coronary Artery Disease
[Gene Polymorphism of 5, 10-methylenetetrahydrofolate reductase as a coronary risk factor]
Coronary Disease
The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease.
COVID-19
Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia?
Craniosynostoses
Methylenetetrahydrofolate reductase C677T variant in Indian children with craniosynostosis: Its role in the pathogenesis, risk of craniosynostosis.
Dementia
Association of the transcobalamin II gene 776C?G polymorphism with Alzheimer's type dementia: dependence on the 5, 10-methylenetetrahydrofolate reductase 1298A?C polymorphism genotype.
Epilepsy
Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura.
Favism
High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms.
Fetal Growth Retardation
Placenta-mediated pregnancy complications are not associated with fetal or paternal factor V Leiden mutation.
Heart Defects, Congenital
Association between 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and congenital heart disease: A meta-analysis.
Hematologic Neoplasms
[A new method for 5, 10-methylenetetrahydrofolate reductase single nucleotide polymorphisms genotyping used to study susceptibility of hematological malignancy]
Homocystinuria
Infantile type of homocystinuria with N5,10-methylenetetrahydrofolate reductase defect.
Homocystinuria
Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency.
Hyperhomocysteinemia
A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population.
Hyperhomocysteinemia
A common mutation in the 5,10-methylenetetrahydrofolate reductase gene as a new risk factor for placental vasculopathy.
Infertility, Male
A Association of MTHFR C677T and MTRR A66G Gene Polymorphisms with Iranian Male Infertility and Its Effect on Seminal Folate and Vitamin B12.
Ischemic Stroke
Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke.
Meningomyelocele
Folate metabolism gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with ADHD in myelomeningocele patients.
methylenetetrahydrofolate reductase [nad(p)h] deficiency
Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency.
Migraine Disorders
Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura.
Migraine Disorders
High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms.
Migraine with Aura
Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura.
Myocardial Infarction
The TT genotype of the methylenetetrahydrofolate reductase C677T gene polymorphism is associated with the extent of coronary atherosclerosis in patients at high risk for coronary artery disease.
Neoplasms
Loss of heterozygosity at the 5,10-methylenetetrahydrofolate reductase locus in human ovarian carcinomas.
Nervous System Diseases
The effects of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction.
Neural Tube Defects
Association of the 677C-->T mutation on the methylenetetrahydrofolate reductase gene in Turkish patients with neural tube defects.
Osteonecrosis
Lack of association of MTHFR gene polymorphisms with the risk of osteonecrosis of the femoral head in a Korean population.
Pre-Eclampsia
Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.
Pre-Eclampsia
Placenta-mediated pregnancy complications are not associated with fetal or paternal factor V Leiden mutation.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Association between MTHFR C677T Polymorphism and Risk of Acute Lymphoblastic Leukemia: A Meta-Analysis Based on 51 Case-Control Studies.
Riboflavin Deficiency
The effect of riboflavin deficiency on methylenetetrahydrofolate reductase (NADPH) (EC 1.5.1.20) and folate metabolism in the rat.
Spinal Dysraphism
[Frequency of C677T polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR) in Chilean mothers of spina bifida cases and controls ]
Starvation
Genetic diversity and population structure of food-borne Staphylococcus carnosus strains.
Stillbirth
Placenta-mediated pregnancy complications are not associated with fetal or paternal factor V Leiden mutation.
Thrombophilia
MTHFR (C677T, A1298C), FV Leiden polymorphisms, and the prothrombin G20210A mutation in arterial ischemic stroke among young tunisian adults.
Thrombophilia
Placenta-mediated pregnancy complications are not associated with fetal or paternal factor V Leiden mutation.
Thrombosis
Methylenetetrahydrofolate reductase gene C677T mutation and plasma homocysteine level in Behçet's disease.
Thrombosis
Prevalence of the C677T methylenetetra- hydrofolate reductase mutation in Thai patients with deep vein thrombosis.
Tuberculosis
bis-Molybdopterin guanine dinucleotide is required for persistence of Mycobacterium tuberculosis in guinea pigs.
Uterine Cervical Neoplasms
Allelic variations in 5, 10-methylenetetrahydrofolate reductase gene and susceptibility to cervical cancer in Indian women.
Venous Thromboembolism
Lack of association of MTHFR gene polymorphisms with the risk of osteonecrosis of the femoral head in a Korean population.
Venous Thrombosis
Methylenetetrahydrofolate reductase gene C677T mutation and plasma homocysteine level in Behçet's disease.
Venous Thrombosis
Prevalence of the C677T methylenetetra- hydrofolate reductase mutation in Thai patients with deep vein thrombosis.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.011
5,10-methylenetetrahydrofolate
recombinant enzyme, with NADPH, pH 7.2
0.012
5,10-methylenetetrahydrofolate
-
NADPH-5,10-methylenetetrahydrofolate-oxidoreductase reaction
0.019
5,10-methylenetetrahydrofolate
-
methylenetetrahydrofolate reductase reaction, pH 6.7
0.021
5,10-methylenetetrahydrofolate
-
methylenetetrahydrofolate reductase reaction
0.0224
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR1-656
0.0255
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR38-644
0.088
5,10-methylenetetrahydrofolate
-
methylenetetrahydrofolate reductase reaction, pH 7.2
0.106
5,10-methylenetetrahydrofolate
-
recombinant chimeric mutant enzyme, with NADH, pH 7.2
0.106
5,10-methylenetetrahydrofolate
recombinant chimeric mutant enzyme, with NADH, pH 7.2
0.152
5,10-methylenetetrahydrofolate
-
recombinant chimeric mutant enzyme, with NADPH, pH 7.2
0.152
5,10-methylenetetrahydrofolate
recombinant chimeric mutant enzyme, with NADPH, pH 7.2
0.287
5,10-methylenetetrahydrofolate
-
recombinant wild-type enzyme, with NADH, pH 7.2
0.038
5-methyltetrahydrofolate
-
5,10-methylenetetrahydrofolate-oxidoreductase reaction
0.0004
methylenetetrahydrofolate
-
recombinant wild-type enzyme, pH 7.2, 4°C
0.0035
NADH
-
recombinant wild-type enzyme, pH 7.2, 4°C, the mutant enzymes all show a Km below 0.0035 mM
0.02
NADH
cosubstrate 5,10-methylenetetrahydrofolate, wild-type, pH 7.2, 25°C
0.14
NADH
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223A, pH 7.2, 25°C
0.236
NADH
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223L, pH 7.2, 25°C
additional information
additional information
-
Km for various dihydropterin derivatives
-
additional information
additional information
-
redox potentials of wild-type and mutant enzymes, kinetic mechanism, and rapid-reaction kinetics for the half-reactions, steady-state kinetics
-
additional information
additional information
Michaelis-Menten kinetics for wild-type and mutant enzymes
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
40.7
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR1-656
51.4
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR38-644
10.4
NADH
cosubstrate 5,10-methylenetetrahydrofolate, wild-type, pH 7.2, 25°C
14
NADH
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223L, pH 7.2, 25°C
21.9
NADH
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223A, pH 7.2, 25°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1817
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR1-656
2015.7
5,10-methylenetetrahydrofolate
pH 6.6, 46°C, enzyme mutant HsMTHFR38-644
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.014
NADH
-
recombinant wild-type enzyme, pH 7.2, 4°C, the mutant enzymes all show a Km below 0.0035 mM
0.455
5,10-methylenetetrahydrofolate
recombinant enzyme, with NADPH, pH 7.2
0.873
5,10-methylenetetrahydrofolate
-
recombinant wild-type enzyme, with NADH, pH 7.2
additional information
additional information
-
dihydropteroylpolyglutamate inhibitors with different numbers of glutamyl residues
-
additional information
additional information
enzyme inhibition kinetics
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0007
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
Homo sapiens
-
-
0.0022
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
Homo sapiens
-
-
0.033
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
Homo sapiens
-
-
0.0018
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
Homo sapiens
-
-
0.0035
N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
0.0012
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
0.0016
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
-
additional information
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
additional information
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
value above 0.048
additional information
N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
Homo sapiens
-
value above 0.05
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
distribution of specific activity in different parts of the central nervous system
additional information
-
specific activity in various patients with enzyme deficiencies
additional information
-
values of healthy and homocysteinemic humans before and after heat inactivation, specific activity of thermolabile variant of enzyme in homozygotes is 50% of normal enzyme
additional information
-
distribution of specific activity in different parts of the central nervous system
additional information
-
specific activity is greater with the monoglutamate substrate than with the pentaglutamate
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.6
6.7
7.2
6.7
-
5-methyltetrahydrofolate and 5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate as substrates
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 9
2% activity remain at pH 5.0, and 6% activity at pH 9.0
5.8 - 8.6
-
about 60% of activity maximum at pH 5.8, about 50% of activity maximum at pH 8.6, menadione reductase activity
6 - 8
-
pH 6: about 70% of activity maximum, pH 8: about 35% of activity maximum with 5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate, about 65% of activity maximum with 5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
6.2 - 7.3
-
half-maximal activity at pH 6.2 and pH 7.3, methylenetetrahydrofolate reductase reaction
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 45
-
methylenetetrahydrofolate reductase reaction, slow increase of activity between 25°C and 45°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
two isoenzymes, encoded by the genes MET12 and MET13
-
-
brenda
-
-
-
brenda
-
392157, 392164, 392165, 392166, 437719, 437721, 437722, 437723, 437725, 654163, 677069, 684226, 684273, 684274, 684280, 684291, 684295, 684297, 684298, 684314, 684428, 684441, 684442, 684465, 684469, 684473, 684738, 684805, 685493, 685860, 685862, 685893, 685894, 685895, 685917, 685988, 685990, 685995, 686128, 686133, 686144, 686149, 686158, 686185, 686240, 686310, 686329
-
-
brenda
-
686343, 686497, 686513, 686515, 686517, 686540, 686572, 686589, 686590, 686592, 686633, 686829, 686835, 686994, 687023, 687066, 687152, 687167, 687170, 687174, 687359, 687832, 687894, 687946, 687957, 688057, 688129, 688135, 688140, 688142, 688184
-
-
brenda
-
688476, 688554, 688562, 688565, 688688, 688704, 688709, 688710, 688715, 688756, 688778, 689009, 689031
-
-
brenda
-
689103, 689111, 689166, 689282, 689284, 689298, 689329, 689330, 689333, 689366, 689729, 689833, 689836, 690042, 690049, 690083, 690112, 690122, 690124, 690162, 690181, 690199, 690212, 697857, 698118, 699849, 702155, 712182, 713042, 724809
-
-
brenda
recombinant enzyme, expression in Escherichia coli, Baculovirus system, or HEK293 cells
-
-
brenda
-
-
-
brenda
a single enzyme with methylenetetrahydrofolate reductase and dopamine methyltransferase activity
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
-
brenda
-
-
684226, 684273, 684280, 684295, 684314, 684428, 684442, 684465, 684469, 684738, 684805, 685493, 685860, 685894, 685917, 685990, 686128, 686133, 686144, 686149, 686185, 686497, 686540, 686589, 686590, 686633, 686994, 687023, 687066, 687167, 687170, 687174, 687359, 687832, 687957, 688129, 688135, 688554, 688704, 688709, 688778, 689009, 689103, 689282, 689284, 689298, 689330, 689333, 689833, 689836, 690042, 690049, 690112, 690122, 690124, 690162, 690212
brenda
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