Information on EC 1.5.1.20 - methylenetetrahydrofolate reductase [NAD(P)H]

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY
1.5.1.20
-
RECOMMENDED NAME
GeneOntology No.
methylenetetrahydrofolate reductase [NAD(P)H]
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
show the reaction diagram
-
-
-
-
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
show the reaction diagram
mechanism
-
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
show the reaction diagram
mechanism, acceptor is free FAD, stereochemistry
-
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
show the reaction diagram
ping-pong bi-bi mechanism, in which NAD(P)+ release precedes the binding of methylenetetrahydrofolate
-
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
show the reaction diagram
substrate binding and catalyic mechanism involve Asp120, half-reaction mechanisms
-
5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H + H+
show the reaction diagram
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
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Carbon fixation pathways in prokaryotes
-
-
folate transformations I
-
-
folate transformations II
-
-
Metabolic pathways
-
-
Microbial metabolism in diverse environments
-
-
N10-formyl-tetrahydrofolate biosynthesis
-
-
One carbon pool by folate
-
-
reductive acetyl coenzyme A pathway
-
-
sulfopterin metabolism
-
-
tetrahydrofolate metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
5-methyltetrahydrofolate:NAD(P)+ oxidoreductase
A flavoprotein (FAD). Menadione can also serve as an electron acceptor.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10-methylenetetrahydrofolate reductase
-
-
5,10-CH2-H4folate reductase
-
-
-
-
5,10-methylenetetrahydrofolate reductase
-
-
-
-
5,10-methylenetetrahydrofolate reductase (FADH2)
-
-
5,10-methylenetetrahydrofolate reductase (NADPH)
-
-
-
-
5,10-methylenetetrahydrofolic acid reductase
-
-
-
-
5,10-methylenetetrahydropteroylglutamate reductase
-
-
-
-
5-methylenetetrahydrofolate:NADP+ oxidoreductase
-
-
5-methyltetrahydrofolate:(acceptor) oxidoreductase
-
-
5-methyltetrahydrofolate:NAD oxidoreductase
-
-
-
-
5-methyltetrahydrofolate:NAD+ oxidoreductase
-
-
-
-
5-methyltetrahydrofolate:NADP+ oxidoreductase
-
-
-
-
EC 1.1.1.171
-
-
formerly
-
EC 1.1.1.68
-
-
formerly
-
EC 1.1.99.15
-
-
formerly
-
MET13
Aspergillus nidulans W-12
-
-
-
methlenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase
-
-
-
-
methylenetetrahydrofolate reductase
-
-
-
-
methylenetetrahydrofolate reductase
Q7CXU3
-
methylenetetrahydrofolate reductase
O67422
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
O80585
-
methylenetetrahydrofolate reductase
Q5B0P7
-
methylenetetrahydrofolate reductase
Q2UEQ8
-
methylenetetrahydrofolate reductase
Q8A146
-
methylenetetrahydrofolate reductase
Q8G652
-
methylenetetrahydrofolate reductase
Q7WQX3
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
Q5I598
-
methylenetetrahydrofolate reductase
Q89UJ7
-
methylenetetrahydrofolate reductase
Q8FZN0
-
methylenetetrahydrofolate reductase
Q17693
-
methylenetetrahydrofolate reductase
Q5AEI0
-
methylenetetrahydrofolate reductase
Q6FU20
-
methylenetetrahydrofolate reductase
Q7VRL4
-
methylenetetrahydrofolate reductase
Q9A6F4
-
methylenetetrahydrofolate reductase
Q7NZF6
-
methylenetetrahydrofolate reductase
Q6J6A1
-
methylenetetrahydrofolate reductase
Q6NGB6
-
methylenetetrahydrofolate reductase
Q8NNM2
-
methylenetetrahydrofolate reductase
Q83A63
-
methylenetetrahydrofolate reductase
Q72DD2
-
methylenetetrahydrofolate reductase
Q54X84
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
Q7NMH7
-
methylenetetrahydrofolate reductase
P42898
-
methylenetetrahydrofolate reductase
Q9L5C1
-
methylenetetrahydrofolate reductase
Q60HE5
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
Q98K87
-
methylenetetrahydrofolate reductase
Q8PZQ4
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
Q9WU20
-
methylenetetrahydrofolate reductase
Q10BJ7
-
methylenetetrahydrofolate reductase
Q9CP31
-
methylenetetrahydrofolate reductase
Q7MYD0
-
methylenetetrahydrofolate reductase
Q7VE38
-
methylenetetrahydrofolate reductase
Q87V72
-
methylenetetrahydrofolate reductase
Q8Y389
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
Q7UNJ7
-
methylenetetrahydrofolate reductase
Q6N3J2
-
methylenetetrahydrofolate reductase
P53128
-
methylenetetrahydrofolate reductase
-
-
methylenetetrahydrofolate reductase
Q10258
-
methylenetetrahydrofolate reductase
Q0SY49
-
methylenetetrahydrofolate reductase
Q92NK1
-
methylenetetrahydrofolate reductase
Q8DQT1
-
methylenetetrahydrofolate reductase
Q4T956
-
methylenetetrahydrofolate reductase
Q72H39
-
methylenetetrahydrofolate reductase
Q9KNP6
-
methylenetetrahydrofolate reductase
Q87L52
-
methylenetetrahydrofolate reductase
Q7MH66
-
methylenetetrahydrofolate reductase
Q7M8S8
-
methylenetetrahydrofolate reductase
Q7ZWU2
-
methylenetetrahydrofolate reductase
Q9PEA7
-
methylenetetrahydrofolate reductase
Q9SE94
-
methylenetetrahydrofolate reductase (NADPH)
-
-
-
-
methylenetetrahydrofolate reductase (NADPH)
-
-
MR
-
-
-
-
MTHFR
-
-
-
-
MTHFR
O67422
-
MTHFR
O80585
-
MTHFR
Q5B0P7
-
MTHFR
Aspergillus nidulans W-12
-
-
-
MTHFR
Q2UEQ8
-
MTHFR
Q5I598
-
MTHFR
Q8FZN0
-
MTHFR
Q5AEI0
-
MTHFR
Q6FU20
-
MTHFR
Q83A63
-
MTHFR
Q7NMH7
-
MTHFR
P42898
-
MTHFR
Q60HE5
-
MTHFR
Q98K87
-
MTHFR
Q8PZQ4
-
MTHFR
Q9WU20
-
MTHFR
Q10BJ7
-
MTHFR
Q9CP31
-
MTHFR
Q87V72
-
MTHFR
Q0SY49
-
MTHFR
Q5SLG6
-
MTHFR
Q72H39
-
MTHFR
Q9KNP6
-
MTHFR
Q7MH66
-
MTHFR
Q7ZWU2
-
MTHFR
Q9PEA7
-
MTHFR
Q9SE94
-
MTHFR2
-
-
-
-
N5,10-methylenetetrahydrofolate reductase
-
-
-
-
N5,N10-methylenetetrahydrofolate reductase
-
-
-
-
NADH:CH2-H4folate oxidoreductase
Q5SLG6
-
nitrate reductase A
-
-
reductase, methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate)
-
-
-
-
reductase, methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide)
-
-
-
-
respiratory nitrate reductase
-
-
methylenetetrahydrofolic acid reductase
-
-
-
-
additional information
-
EC 1.7.99.5 included with EC 1.5.1.20
CAS REGISTRY NUMBER
COMMENTARY
71822-25-8
-
9028-69-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ecotype Columbia, expression in Saccharomyces cerevisiae
-
-
Manually annotated by BRENDA team
gene met13
-
-
Manually annotated by BRENDA team
Aspergillus nidulans W-12
-
-
-
Manually annotated by BRENDA team
Bradyrhizobium japonicum USDA110
USDA110
-
-
Manually annotated by BRENDA team
guinea pig
-
-
Manually annotated by BRENDA team
Cercocebus sp.
monkey
-
-
Manually annotated by BRENDA team
strain ATCC 23439
-
-
Manually annotated by BRENDA team
strain 113-3
-
-
Manually annotated by BRENDA team
Escherichia coli 113-3
strain 113-3
-
-
Manually annotated by BRENDA team
healthy men and women aged 19-63 years
-
-
Manually annotated by BRENDA team
patients with bipolar disorder
-
-
Manually annotated by BRENDA team
patients with colorectal cancer
-
-
Manually annotated by BRENDA team
patients with enzyme deficiency
-
-
Manually annotated by BRENDA team
patients with Parkinson's disease
-
-
Manually annotated by BRENDA team
patients with rheumatoid arthritis
-
-
Manually annotated by BRENDA team
patients with spina bifida
UniProt
Manually annotated by BRENDA team
patients with systemic sclerosis
-
-
Manually annotated by BRENDA team
pediatric patients with acute lymphoblastic leukemia
-
-
Manually annotated by BRENDA team
recombinant enzyme, expression in Escherichia coli, Baculovirus system, or HEK293 cells
-
-
Manually annotated by BRENDA team
expression in Saccharomyces cerevisiae
-
-
Manually annotated by BRENDA team
formerly Mesorhizobium loti
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
mouse model of mild Mthfr deficiency
-
-
Manually annotated by BRENDA team
adult male Sprague-Dawley rats, fed a Purina lab chow diet
-
-
Manually annotated by BRENDA team
gene met13
SwissProt
Manually annotated by BRENDA team
strain DAY4, two isoenzymes, encoded by the genes MET12 and MET13
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae DAY4
strain DAY4, two isoenzymes, encoded by the genes MET12 and MET13
-
-
Manually annotated by BRENDA team
genes met9 and met11
-
-
Manually annotated by BRENDA team
synonym Sinorhizobium meliloti
UniProt
Manually annotated by BRENDA team
7 to 8-d-old piglets, milk from lactating sows
-
-
Manually annotated by BRENDA team
a single enzyme with methylenetetrahydrofolate reductase and dopamine methyltransferase activity
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
expression in Saccharomyces cerevisiae
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
mutations in the enzyme lead to hyperhomocysteinemia. A C677T polymorphism is associated with an increased risk for the development of cardiovascular disease, Alzheimer's disease, and depression in adults and of neural tube defects in the fetus
metabolism
-
the enzyme plays a key role in folate metabolism and in the homeostasis of homocysteine
physiological function
-
enzyme activity is involved in the plasma membrane redox system required for pigment biosynthesis in filamentous fungi
physiological function
Aspergillus nidulans W-12, Fusarium graminearum PH-1
-
enzyme activity is involved in the plasma membrane redox system required for pigment biosynthesis in filamentous fungi
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
show the reaction diagram
Q5SLG6
-
-
-
r
(6R,S)-5,10-methylenetetrahydrofolate + ?
?
show the reaction diagram
-
-
-
-
-
(6R,S)-5,10-methylenetetrahydrofolate + ?
?
show the reaction diagram
-
-
-
-
-
(6R,S)-5,10-methylenetetrahydrofolate + ?
?
show the reaction diagram
-
assay at 25C
-
-
?
5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate + reduced acceptor
(+)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate + oxidized acceptor
show the reaction diagram
-
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
menadione as acceptor for 5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate formation
?
5,10-methylenetetrahydrofolate + acceptor
5-methyltetrahydrofolate + reduced acceptor
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + acceptor
5-methyltetrahydrofolate + reduced acceptor
show the reaction diagram
-
-
-
-
ir
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
first step of conversion of 5,10-methylenetetrahydrofolate to methionine
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
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
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
Escherichia coli 113-3
-
-
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
Escherichia coli 113-3
-
biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
-
-
?
5,10-methylenetetrahydrofolate + NAD(P)H
5-methyltetrahydrofolate + NAD(P)+
show the reaction diagram
-
NADH is the preferred cofactor of the plant enzyme
-
-
r
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
Q9SE94
folate-mediated one-carbon metabolism
-
r
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
folate-mediated one-carbon metabolism
-
r
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
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
-
-
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
physiological direction: 5-methyltetrahydrofolate formation, inhibition by S-adenosylmethionine functions as a feedback-type metabolic regulation in vivo
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
ir
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
P53128
-
-
-
r
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
ping pong bi bi mechanism
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
ferricyanide, dichlorophenolindophenol and cytochrome c can act as electron acceptors
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
equilibrium far on the side of methyltetrahydrofolate formation
-
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
equilibrium far on the side of methyltetrahydrofolate formation
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
ping pong kinetics
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
enzyme catalyzes the reduction of quinoid dihydropterins without a 5-substituent
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
enzyme also catalyzes the NADPH-linked reduction of quinoid dihydrofolate and dihydropterin derivates
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
specific for (+)-diastereoisomer
-
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
specific for (+)-diastereoisomer
-
-
-
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
physiological NADPH-CH2-H4folate oxidoreductase activity
5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
Saccharomyces cerevisiae, Saccharomyces cerevisiae DAY4
-
enzyme encoded by MET13 produces 5-methyltetrahydrofolate used for methylation of homocysteine for methionine biosynthesis in vivo, NADPH is the likely natural reductant
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
branch point in folate metabolism
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
initial enzyme in pathway leading to synthesis of S-adenosylmethionine
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
first step in biosynthesis of methyl groups
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
overview: role in incorporation of methyltetrahydrofolate into cellular metabolism
-
-
?
5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
ir
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
P42898
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
ir
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9WU20
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
P53128
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q17693
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q4T956
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q5I598
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q60HE5
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q10BJ7
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9SE94
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7ZWU2
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
O80585
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q0SY49
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9L5C1
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q72H39
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q6J6A1
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q8NNM2
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7VRL4
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7CXU3
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
O67422
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q8A146
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7WQX3
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q89UJ7
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q8FZN0
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9A6F4
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7NZF6
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q6NGB6
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q83A63
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q72DD2
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7NMH7
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q98K87
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q8PZQ4
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9CP31
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7MYD0
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7UNJ7
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7VE38
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q87V72
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q8Y389
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q6N3J2
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q92NK1
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q8DQT1
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9KNP6
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q87L52
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7MH66
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q7M8S8
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q8G652
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9PEA7
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q5AEI0
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q10258
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q6FU20
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q2UEQ8
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q5B0P7
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q54X84
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
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
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced acceptor is FADH2, 5,10-methylene-5,6,7,8-tetrahydropteroylmonoglutamate as substrate
product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
equilibrium lies far in favor of 5-methyltetrahydrofolate formation
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
equilibrium lies far in favor of 5-methyltetrahydrofolate formation
product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9SE94
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: menadione as electron acceptor
product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
prefers NADH as reductant
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: FAD, rubredoxin, benzyl viologen and methylene blue as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
reverse reaction: FAD, rubredoxin, benzyl viologen and methylene blue as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced ferredoxin as reduced acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: reduced ferredoxin as reduced acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: NADPH as reduced acceptor
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: NADPH as reduced acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: NADH as reduced acceptor
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: NADH as reduced acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: NADH as reduced acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: NADH as reduced acceptor
product is (+)-5-methyl-5,6,7,8-tetrahydropteroylmonoglutamate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: NADPH as reduced acceptor causes irreversible reduction of the flavin coenzyme FAD
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Q9SE94
forward reaction: strong preference of NADH over NADPH
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
forward reaction: strong preference of NADH over NADPH
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
supply of the folate needed for the metabolism of homocysteine: 5-methyltetrahydrofolate is required for the methylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
homocysteine metabolism
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
homocysteine metabolism, physiological direction is the 5-methyltetrahydrofolate formation
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
remethylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
remethylation of homocysteine to methionine
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Saccharomyces cerevisiae DAY4
-
equilibrium lies far in favor of 5-methyltetrahydrofolate formation, forward reaction: NADPH as reduced acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Escherichia coli 113-3
-
forward reaction: reduced acceptor is FADH2, reverse reaction: menadione as electron acceptor
-
r
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
Escherichia coli 113-3
-
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, forward reaction: reduced acceptor is FADH2
-
r
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
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
-
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
physiological important reaction: enzyme catalyzes reduction of 5,10-methylenetetrahydrofolate with reduced ferredoxin
-
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
physiological important reaction: enzyme catalyzes reduction of 5,10-methylenetetrahydrofolate with reduced ferredoxin
-
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
enzyme is part of synthesis pathway of acetate from CO2 via a unique tetrahydrofolate-corrinoid pathway
-
?
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH
show the reaction diagram
-
-
-
-
r
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
show the reaction diagram
-
-
-
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
show the reaction diagram
-
-
-
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
show the reaction diagram
-
-
-
-
?
5-methyltetrahydrofolate + oxidized menadione
5,10-methylenetetrahydrofolate + reduced menadione
show the reaction diagram
-
ping pong kinetics
-
-
?
NADH + menadione
NAD+ + reduced menadione
show the reaction diagram
-
-
-
-
-
NADPH + H+ + menadione
NADP+ + menadiol
show the reaction diagram
-
-
-
?
NADPH + H+ + menadione
NADP+ + menadiol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + menadione
NADP+ + menadiol
show the reaction diagram
-
ping pong kinetics
-
-
?
nitrate + reduced acceptor
nitrite + acceptor
show the reaction diagram
Bradyrhizobium japonicum, Bradyrhizobium japonicum USDA110
-
the enzyme is responsible for anaerobic growth of Bradyrhizobium japonicum under nitrate-respiring conditions
-
-
?
nitrate + reduced benzyl viologen
nitrite + benzyl viologen
show the reaction diagram
-
-
-
-
?
nitrate + reduced benzyl viologen
nitrite + benzyl viologen
show the reaction diagram
-
-
-
-
-
nitrate + reduced benzyl viologen
nitrite + benzyl viologen
show the reaction diagram
Bradyrhizobium japonicum USDA110
-
-
-
-
?
nitrate + reduced methyl viologen
nitrite + methyl viologen
show the reaction diagram
-
-
-
-
?
nitrate + reduced methyl viologen
nitrite + methyl viologen
show the reaction diagram
Bradyrhizobium japonicum, Bradyrhizobium japonicum USDA110
-
-
-
-
?
5-methyltetrahydropteroylmonoglutamate + 5,10-methylenetetrahydropteroylhexaglutamate
5,10-methylenetetrahydropteroylmonoglutamate + 5-methyltetrahydropteroylhexaglutamate
show the reaction diagram
-
-
-
r
additional information
?
-
-
no direct activity with pyridine nucleotides
-
-
-
additional information
?
-
-
no direct activity with pyridine nucleotides
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
not as electron donor: reduced rubredoxin
-
-
-
additional information
?
-
-
reverse reaction: not NADP+ as acceptor
-
-
-
additional information
?
-
-
reverse reaction: menadione and 2,6-dichlorophenolindophenol and NADP+ are not effective as electron acceptor
-
-
-
additional information
?
-
-
in patients with defects in the enzyme the homocysteine concentrations are increased, hyperhomocysteinemia elevates the risk for cardiovascular disease
-
-
-
additional information
?
-
-
the enzyme is responsible for the first step in the denitrification process
-
-
-
additional information
?
-
Saccharomyces cerevisiae DAY4
-
reverse reaction: menadione and 2,6-dichlorophenolindophenol and NADP+ are not effective as electron acceptor
-
-
-
additional information
?
-
Escherichia coli 113-3
-
no direct activity with pyridine nucleotides
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(6R)-5,10-methylenetetrahydrofolate + NAD(P)H + H+
(6S)-5-methyltetrahydrofolate + NAD(P)+
show the reaction diagram
Q5SLG6
-
-
-
r
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
first step of conversion of 5,10-methylenetetrahydrofolate to methionine
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
-
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
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
Escherichia coli 113-3
-
-
-
-
?
5,10-methylenetetrahydrofolate + FADH2
5-methyltetrahydrofolate + FAD
show the reaction diagram
Escherichia coli 113-3
-
biosynthesis of 5-methyltetrahydrofolate, a donor of methyl groups of methionine
-
-
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NAD(P)H + H+
5-methyltetrahydrofolate + NAD(P)+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
-
-
-
-
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
Q9SE94
folate-mediated one-carbon metabolism
-
r
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
folate-mediated one-carbon metabolism
-
r
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
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
-
-
?
5,10-methylenetetrahydrofolate + NADH
5-methyltetrahydrofolate + NAD+
show the reaction diagram
-
physiological direction: 5-methyltetrahydrofolate formation, inhibition by S-adenosylmethionine functions as a feedback-type metabolic regulation in vivo
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
physiological NADPH-CH2-H4folate oxidoreductase activity
5-methyltetrahydrofolate is the major methyl donor for the conversion of homocysteine to methionine
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
enzyme encoded by MET13 produces 5-methyltetrahydrofolate used for methylation of homocysteine for methionine biosynthesis in vivo, NADPH is the likely natural reductant
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
branch point in folate metabolism
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
initial enzyme in pathway leading to synthesis of S-adenosylmethionine
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
first step in biosynthesis of methyl groups
-
-
?
5,10-methylenetetrahydrofolate + NADPH
?
show the reaction diagram
-
overview: role in incorporation of methyltetrahydrofolate into cellular metabolism
-
-
?
5,10-methylenetetrahydrofolate + NADPH
5-methyltetrahydrofolate + NADP+
show the reaction diagram
Saccharomyces cerevisiae DAY4
-
enzyme encoded by MET13 produces 5-methyltetrahydrofolate used for methylation of homocysteine for methionine biosynthesis in vivo, NADPH is the likely natural reductant
-
?
5,10-methylenetetrahydrofolate + NADPH + H+
5-methyltetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
supply of the folate needed for the metabolism of homocysteine: 5-methyltetrahydrofolate is required for the methylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
homocysteine metabolism
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
homocysteine metabolism, physiological direction is the 5-methyltetrahydrofolate formation
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
remethylation of homocysteine to methionine
-
?
5,10-methylenetetrahydrofolate + reduced acceptor
5-methyltetrahydrofolate + oxidized acceptor
show the reaction diagram
-
remethylation of homocysteine to methionine
5-methyltetrahydrofolate is the main form of circulating folate
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
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
-
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
physiological important reaction: enzyme catalyzes reduction of 5,10-methylenetetrahydrofolate with reduced ferredoxin
-
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
physiological important reaction: enzyme catalyzes reduction of 5,10-methylenetetrahydrofolate with reduced ferredoxin
-
?
5,10-methylenetetrahydrofolate + reduced ferredoxin
5-methyltetrahydrofolate + oxidized ferredoxin
show the reaction diagram
-
enzyme is part of synthesis pathway of acetate from CO2 via a unique tetrahydrofolate-corrinoid pathway
-
?
5-methyltetrahydrofolate + NAD+
5,10-methylenetetrahydrofolate + NADH
show the reaction diagram
-
-
-
-
r
nitrate + reduced acceptor
nitrite + acceptor
show the reaction diagram
Bradyrhizobium japonicum, Bradyrhizobium japonicum USDA110
-
the enzyme is responsible for anaerobic growth of Bradyrhizobium japonicum under nitrate-respiring conditions
-
-
?
5-methyltetrahydrofolate + NADP+
5,10-methylenetetrahydrofolate + NADPH
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
in patients with defects in the enzyme the homocysteine concentrations are increased, hyperhomocysteinemia elevates the risk for cardiovascular disease
-
-
-
additional information
?
-
-
the enzyme is responsible for the first step in the denitrification process
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
each subunit of the dimer or trimer contains bound FAD; flavoprotein
FAD
-
each subunit contains noncovalently bound FAD; flavoprotein
FAD
-
required
FAD
-
flavoprotein
FAD
-
flavoprotein with non-covalently bound FAD
FAD
-
non covalently bound
FAD
-
enzyme-bound FAD as coenzyme; flavoprotein, oxidized acceptor in reverse reaction
FAD
-
1.7 molecules enzyme-bound FAD per enzyme molecule; flavoprotein, oxidized acceptor in reverse reaction
FAD
-
enzyme-bound FAD; flavoprotein, oxidized acceptor in reverse reaction
FAD
-
flavoprotein, oxidized acceptor in reverse reaction
FAD
-
requires FAD as cofactor
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; flavoprotein with FAD as cofactor
FAD
-
flavoprotein with FAD as cofactor
FAD
-
flavoprotein with FAD as cofactor
FAD
-
enzyme-bound
FAD
-
redox properties of enzyme-bound FAD are influenced by Asp120, which electrostatically stabilizes putative 5-iminium cation intermediate during catalysis
FAD
O67422
-
FAD
Q2UEQ8
-
FAD
Q5I598
-
FAD
Q8FZN0
-
FAD
Q5AEI0
-
FAD
Q6FU20
-
FAD
Q83A63
-
FAD
Q98K87
-
FAD
Q9WU20
-
FAD
Q10BJ7
-
FAD
Q0SY49
-
FAD
Q9KNP6
-
FAD
Q7MH66
-
FAD
Q7ZWU2
-
FAD
Q9PEA7
-
FAD
Q9SE94
-
FAD
Q5SLG6
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
FADH2
-
flavoprotein, reduced acceptor in forward reaction
FADH2
-
flavoprotein, reduced acceptor in forward reaction
FADH2
-
flavoprotein, reduced acceptor in forward reaction
FADH2
-
-
flavin
-
flavin-dependent enzyme
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
NAD+
-
recombinant wild-type and chimeric mutant enzymes
NAD+
P53128
only active with the chimeric mutant enzyme, not with the wild-type
NADH
-
low activity
NADH
-
strong preference of NADH over NADPH as reductant
NADH
Q9SE94
strong preference of NADH over NADPH as reductant
NADH
-
recombinant wild-type and chimeric mutant enzymes
NADH
P53128
only active with the chimeric mutant enzyme, not with the wild-type
NADH
-
dual-cofactor specificity with NADH and NADPH under physiological conditions
NADH
-
-
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
-
specific for
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
P53128
dependent on
NADPH
-
dual-cofactor specificity with NADH and NADPH under physiological conditions
NADPH
-
the optimum concentration is 1.2 mM
NADPH
Q5SLG6
-
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
additional information
-
no direct activity with pyridine nucleotides: NADH, NADPH
-
additional information
-
no direct activity with pyridine nucleotides: NADH, NADPH
-
additional information
P53128
wild-type shows no activity with NADH/NAD+
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Iron
-
15.2 molecules iron per enzyme molecule, enzyme contains iron-sulfur clusters
Iron
-
the catalytic subunit NarG contains a novel [4Fe-4S] cluster with a high-spin ground state
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-sulfur centre
-
enzyme contains 15.2 molecules iron and 19.5 molecules acid-labile sulfur as 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
Zinc
-
2.3 molecules zinc per enzyme molecule
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
-
no evidence for participation of heavy metals ions in catalytic process
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
inhibits at high concentrations
2,4-dihydroxyphenylacetic acid
-
at 0.01 M
5,10-methylenetetrahydrofolate
-
substrate inhibition
5,10-methylenetetrahydrofolate
P53128
substrate inhibition
5,10-methylenetetrahydrofolate
-
-
dicoumarol
-
inhibits menadione reductase activity only
diethyldicarbonate
-
20 mM NADP+ and 20 mM NAD+ partially protected the enzyme against inactivation whereas 20 mM nicotinamide gives complete protection
dihydrofolate
-
competitive with respect to 5,10-methylenetetrahydrofolate and uncompetitive with respect to NADPH
dihydrofolate
-
-
dihydropteroylhexaglutamate
-
-
dihydropteroylpolyglutamate
-
-
-
dihydropteroylpolyglutamate
-
most potent inhibitor is dihydropteroylhexaglutamate
-
folylpolyglutamate
-
overview
-
LY309887
-
i.e. 6R-2,5-thienyl-5,10-dideazatetrahydrofolate monoglutamate
menadione
-
inhibits enzyme activity in yeast extracts
Mersalyl
-
80% inhibition at 1 mM
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-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
-
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
-
N-bromosuccinimide
-
inactivates the enzyme by modification of tryptophan
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
-
-
NADH
-
substrate inhibition above 1 mM
NADPH
-
100 mM
p-chloromercuribenzoate
-
60% inhibition of the methylenetetrahydrofolate reductase activity at 0.04 mM, 83% inhibition of the menadione reductase activity at 0.04 mM
Phenylglyoxal
-
-
Polyglutamate analogues
-
-
-
S-adenosyl-L-methionine
P53128
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-adenosyl-L-methionine
-
allosteric inhibition and control of phosphorylation
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
-
inhibition of the enzyme in crude extracts from fresh liver biopsies, but not after purification from cadaver liver
S-adenosylmethionine
-
0.05 mM
S-adenosylmethionine
-
inhibits both the reduction of the enzyme-bound flavin by 5-methyltetrahydrofolate and the reoxidation of reduced enzyme by 5,10-methylenetetrahydrofolate
S-adenosylmethionine
-
allosteric 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
-
in vivo feedback-inhibition
S-adenosylmethionine
-
-
S-adenosylmethionine
-
strong, reversible allosteric inhibition, prevented by S-adenosylhomocysteine
S-adenosylmethionine
-
-
tetrahydrofolate
-
-
methylenetetrahydrofolate
-
-
additional information
-
residues essential for enzyme activity: arginine, histidine, tryptophan
-
additional information
-
vitamin B12 and methionine can repress enzyme biosynthesis
-
additional information
-
not inhibited by S-adenosylmethionine
-
additional information
Q9SE94
not inhibited by S-adenosylmethionine
-
additional information
-
gene contains a putative S-adenosylmethionione binding sequence, that is inhibitory in eukaryotic MTHFR
-
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
-
not inhibitory: S-adenosyl-L-methionine, no substrate inhibition up to 0.25 mM
-
additional information
-
inhibiting MTHFR with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
A23187
-
treatment of cells results in increase in enzyme mRNA and protein
homocysteine
-
treatment of cells results in increase in enzyme mRNA and protein
S-adenosylmethionine
-
stimulates
thapsigargin
-
treatment of cells results in increase in enzyme mRNA and protein
tunicamycin
-
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
inositol-requiring enzyme-1
-
the induction of MTHFR was also observed after overexpression of inositol-requiring enzyme-1
-
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; 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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003
(+)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
0.023
(+)-5-methyltetrahydrofolate
-
-
0.18
(6R)-5,10-methylenetetrahydrofolate
Q5SLG6
at pH 7.0 and 50C
0.0005
5,10-methylenetetrahydrofolate
-
wild-type enzyme
0.0005
5,10-methylenetetrahydrofolate
-
wild-type, pH 7.2, 25C
0.0039
5,10-methylenetetrahydrofolate
-
-
0.008
5,10-methylenetetrahydrofolate
-
mutant F223L, pH 7.2, 25C
0.011
5,10-methylenetetrahydrofolate
P53128
recombinant enzyme, with NADPH, pH 7.2
0.012
5,10-methylenetetrahydrofolate
-
NADPH-5,10-methylenetetrahydrofolate-oxidoreductase reaction
0.019
5,10-methylenetetrahydrofolate
-
-
0.019
5,10-methylenetetrahydrofolate
-
methylenetetrahydrofolate reductase reaction, pH 6.7
0.021
5,10-methylenetetrahydrofolate
-
methylenetetrahydrofolate reductase reaction
0.026
5,10-methylenetetrahydrofolate
-
-
0.027
5,10-methylenetetrahydrofolate
-
D120N mutant enzyme
0.0703
5,10-methylenetetrahydrofolate
-
at pH 6.8 and 37C
0.088
5,10-methylenetetrahydrofolate
-
methylenetetrahydrofolate reductase reaction, pH 7.2
0.093
5,10-methylenetetrahydrofolate
-
mutant F223A, pH 7.2, 25C
0.106
5,10-methylenetetrahydrofolate
-
recombinant chimeric mutant enzyme, with NADH, pH 7.2
0.106
5,10-methylenetetrahydrofolate
P53128
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
P53128
recombinant chimeric mutant enzyme, with NADPH, pH 7.2
0.287
5,10-methylenetetrahydrofolate
-
recombinant wild-type enzyme, with NADH, pH 7.2
0.019
5-methyltetrahydrofolate
-
-
0.038
5-methyltetrahydrofolate
-
5,10-methylenetetrahydrofolate-oxidoreductase reaction
0.06 - 0.08
5-methyltetrahydrofolate
-
fresh extract
0.085
5-methyltetrahydrofolate
-
wild-type enzyme
0.16
5-methyltetrahydrofolate
-
D120N mutant enzyme
0.0019
5-methyltetrahydropteroylhexaglutamate
-
-
0.033
5-methyltetrahydropteroylmonoglutamate
-
-
11.1
benzyl viologen
-
-
0.12
DL-5-methyltetrahydrofolate
-
-
0.0004
methylenetetrahydrofolate
-
recombinant wild-type enzyme, pH 7.2, 4C
0.017
methylenetetrahydrofolate
-
recombinant mutant D120N, pH 7.2, 4C
0.043
methylenetetrahydrofolate
-
recombinant mutant D120S, pH 7.2, 4C
0.099
methylenetetrahydrofolate
-
recombinant mutant D120A, pH 7.2, 4C
0.142
methylenetetrahydrofolate
-
recombinant mutant D120K, pH 7.2, 4C
0.0027
NADH
-
recombinant wild-type enzyme, pH 7.2
0.0028
NADH
-
recombinant chimeric mutant enzyme, pH 7.2
0.0028
NADH
P53128
recombinant chimeric mutant enzyme, pH 7.2
0.0035
NADH
-
recombinant wild-type enzyme, pH 7.2, 4C, the mutant enzymes all show a Km below 0.0035 mM
0.005
NADH
-
D120N mutant enzyme
0.017
NADH
-
-
0.02
NADH
-
wild-type enzyme
0.02
NADH
-
cosubstrate 5,10-methylenetetrahydrofolate, wild-type, pH 7.2, 25C
0.066
NADH
-
cosubstrate menadione, wild-type, pH 7.2, 25C
0.085
NADH
-
reduction of menadione
0.14
NADH
-
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223A, pH 7.2, 25C
0.236
NADH
-
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223L, pH 7.2, 25C
0.31
NADH
-
methylenetetrahydrofolate reductase reaction
0.47
NADH
-
cosubstrate menadione, mutant F223L, pH 7.2, 25C
0.585
NADH
-
cosubstrate menadione, mutant F223A, pH 7.2, 25C
0.0073
NADPH
-
recombinant chimeric mutant enzyme, pH 7.2
0.0073
NADPH
P53128
recombinant chimeric mutant enzyme, pH 7.2
0.016
NADPH
-
-
0.016
NADPH
-
5,10-methylenetetrahydrofolate reductase reaction, pH 7.2
0.017
NADPH
-
NADPH-menadione oxidoreductase reaction
0.021
NADPH
P53128
recombinant enzyme, pH 7.2
0.028
NADPH
-
NADPH-menadione oxidoreductase reaction
0.03
NADPH
-
-
0.033
NADPH
-
methylenetetrahydrofolate reductase reaction
0.049
NADPH
-
reduction of menadione
0.187
methylenetetrahydrofolate
-
recombinant mutant D120V, pH 7.2, 4C
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
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.007
methylenetetrahydrofolate
-
recombinant mutant D120N, pH 7.2, 4C
0.011
methylenetetrahydrofolate
-
recombinant mutant D120K, pH 7.2, 4C
0.017
methylenetetrahydrofolate
-
recombinant mutant D120V, pH 7.2, 4C
0.02
methylenetetrahydrofolate
-
recombinant mutant D120S, pH 7.2, 4C
0.022
methylenetetrahydrofolate
-
recombinant mutant D120A, pH 7.2, 4C
2.2
methylenetetrahydrofolate
-
recombinant wild-type enzyme, pH 7.2, 4C
10.4
NADH
-
cosubstrate 5,10-methylenetetrahydrofolate, wild-type, pH 7.2, 25C
14
NADH
-
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223L, pH 7.2, 25C
21.9
NADH
-
cosubstrate 5,10-methylenetetrahydrofolate, mutant F223A, pH 7.2, 25C
22
NADH
-
cosubstrate menadione, mutant F223A, pH 7.2, 25C
23.5
NADH
-
-
31
NADH
-
cosubstrate menadione, mutant F223L, pH 7.2, 25C
52
NADH
-
phosphate buffer
55
NADH
-
cosubstrate menadione, wild-type, pH 7.2, 25C
87
NADH
-
Tris buffer
160
NADH
-
-
26.7
NADPH
-
-
74
NADPH
-
phosphate buffer
140
NADPH
-
Tris buffer
160
NADPH
-
-
50
methylenetetrahydrofolate
-
-
additional information
additional information
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04 - 0.051
(+)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
-
-
0.16
5,10-methylenetetrahydrofolate
-
mutant F223L, pH 7.2, 25C
0.32
5,10-methylenetetrahydrofolate
-
wild-type, pH 7.2, 25C
0.455
5,10-methylenetetrahydrofolate
P53128
recombinant enzyme, with NADPH, pH 7.2
0.873
5,10-methylenetetrahydrofolate
-
recombinant wild-type enzyme, with NADH, pH 7.2
0.0065
dihydrofolate
-
-
0.000013
dihydropteroylhexaglutamate
-
-
0.014
NADH
-
recombinant wild-type enzyme, pH 7.2, 4C, the mutant enzymes all show a Km below 0.0035 mM
0.2
S-adenosylmethionine
-
-
0.061
methylenetetrahydrofolate
-
recombinant wild-type enzyme, pH 7.2, 4C
additional information
additional information
-
dihydropteroylpolyglutamate inhibitors with different numbers of glutamyl residues
-
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
-
-
0.0022
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
-
-
0.033
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)glutamic acid
-
-
0.0035
N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
0.0012
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
-
-
0.0018
N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
-
-
additional information
N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
value above 0.048
0.0016
N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
-
additional information
N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
-
value above 0.05
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000424
-
liver homogenate
0.000094
-
wild-type, cell extract
0.00022
Cercocebus sp.
-
reverse reaction
0.000231
-
brain homogenate
0.00029
Cercocebus sp.
-
forward reaction
0.00071
-
forward reaction
0.001
-
reverse reaction
0.0017
-
muscle
0.0045
-
brain
0.0048
-
intestine
0.0082
-
kidney
0.0089
-
pancreas
0.0106
-
liver
0.1
-
-
0.367
-
-
0.413
-
-
1.2
-
-
6.92
-
recombinant enzyme
12.4
-
recombinant enzyme
153
-
-
additional information
-
different assay methods
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
-
-
additional information
-
specific activity is greater with the monoglutamate substrate than with the pentaglutamate
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
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.3 - 6.4
-
formation of 5-methyltetrahydrofolate
6.3 - 6.9
-
-
6.5
-
NADPH-tetrahydrofolate oxidoreductase activity
6.6 - 6.7
-
methylenetetrahydrofolate reductase reaction
6.6
-
methyltetrahydrofolate-menadione oxidoreductase activity
6.7
-
5-methyltetrahydrofolate and 5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate as substrates
6.8
-
-
7
-
assay at
7.1
-
menadione reductase reaction
7.2
-
NADPH-menadione oxidoreductase activity
7.2
-
assay at
7.2
P53128
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
Q9SE94
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 45
-
methylenetetrahydrofolate reductase reaction, slow increase of activity between 25C and 45C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Q9SE94
-
Manually annotated by BRENDA team
Q9SE94
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
66000
-
dimeric enzyme, gel filtration
654695
74500
-
calculated from amino acid sequence
392151
75000
-
SDS-PAGE
392157
77300
-
SDS-PAGE
392151, 392155
108000
-
A177V mutant enzyme, gel filtration
392163
124000
-
determination at pH 9, alpha2,beta2 enzyme form, PAGE
437714
133000
-
tetrameric enzyme, gel filtration
654695
136000
-
scanning transmission electron microscopy
392155
141000
-
gel filtration
437724
150000
-
gel filtration
392157
170000 - 190000
-
gel filtration, single enzyme with methylenetetrahydrofolate reductase and dopamine methyltransferase activity
392150
190000
-
wild type enzyme, gel filtration
392163
210000
-
gel filtration
392151
237000
-
gel filtration
437713
237000
-
determination at pH 7.4, alpha4,beta4 enzyme form; gel filtration
437714
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
Q9SE94
x * 66400, calculated from the nucleotide sequence
?
-
x * 69000, met9, SDS-PAGE, x *72100, met11, SDS-PAGE
?
-
napA encodes the catalytic subunit, the napB gene product is a soluble dihaem c and the napC gene product is a membrane-anchored tetrahaem c-type cytochrome, napE encodes a transmembrane protein of unknown function, the napD gene product is a soluble protein which is assumed to play a role in the maturation of NapA
?
-
x * 34800, calculated
?
-
x * 77000, SDS-PAGE, x * 70000, SDS-PAGE of MTHFR mutant c.523G>A or mutant c.1166G>A
?
Bradyrhizobium japonicum USDA110
-
napA encodes the catalytic subunit, the napB gene product is a soluble dihaem c and the napC gene product is a membrane-anchored tetrahaem c-type cytochrome, napE encodes a transmembrane protein of unknown function, the napD gene product is a soluble protein which is assumed to play a role in the maturation of NapA
-
dimer
-
-
dimer
-
2 * 66000, SDS-PAGE
dimer
-
2 * 77300, SDS-PAGE, gel filtration
dimer
-
2 * 77000
dimer
-
dimer or trimer, 2 or 3 * 77300, SDS-PAGE
dimer
-
2 * 75000, SDS-PAGE and inhibition studies
dimer
-
smallest functional unit of the enzyme
heterodimer
Q5SLG6
x-ray crystallography
octamer
-
alpha4,beta4, 4 * 26000 + 4 * 35000, SDS-PAGE
octamer
-
determined at pH 7.4
tetramer
-
gel filtration
tetramer
-
alpha2,beta2, 2 * 26000 + 2 * 35000, determined at pH 9, SDS-PAGE
tetramer
-
composed of 2 active dimers
homotetramer
-
4 * 33000
additional information
-
alterations in the hydrophobic interactions by 1 M urea lead to dissociation of the native tetramer, resulting in stabilization of enzymatically active holoenzyme dimers, at 3 M urea followed by unfolding of the dimers to denatured monomers along with dissociation of FAD from the enzyme subunits, alterations of the electrostatic interactions by 1.2 M NaCl lead to dissociation of the enzyme into inactive, partially denatured dimers
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
treatment by alkaline phosphatase removes seven phosphoryl groups from enzyme. Treated enzyme is more active than native enzyme and less sensitive to inhibition by S-adenosylmethionie
additional information
-
protein sequence shows no obvious intracellular targeting sequences
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
His-tagged wild-type and mutant E28Q
-
ligand-free mutant F223L and mutant F223L/E28Q in complex with methylenetetrahydrofolate, to 1.65 and 1.7 A resolution, respectively. folate is bound in a catalytically competent conformation, and L223 undergoes a conformational change similar to that observed for F223 in the E28Q-methylenetetrahydrofolate structure
-
mutant A177V, free and in complex with 5,10-dideazafolate analogue LY309887
-
hanging-drop vapor diffusion method. Structure of proteolyzed form of recombinant NapB at 1.25 A resolution
-
crystal structure determined at a resolution of 3.2 A
-
hanging drop vapor diffusion method, using 0.1 M sodium acetate buffer (NaOAc, pH 4.3,4.5), 1 M lithium chloride, 10% (w/v) polyethylene glycol 6000, 10-20% (v/v) glycerol, and 2-5% (v/v) dioxane, at 20C
Q5SLG6
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.1 - 7.6
-
at this pH-range enzyme is more stable in Tris-HCl than in triethanolamine-HCl or phosphate buffers
437714
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
-
5 min, 17% loss of activity
437721
45
-
inactivation above
392149
46
-
5 min, 53% loss of activity
437721
49
-
5 min, 70% loss of activity
437721
51
-
dimeric enzyme, 50% inactivatin at pH 7.2
654695
58
-
tetrameric enzyme, 50% inactivatin at pH 7.2
654695
additional information
-
activity of enzyme from healthy and homocysteinemic humans after heat inactivation, the latter with a more thermolabile enzyme: residual activity in homozygotes is lower than 30% compared with 50% in control subjects
437721
additional information
-
thermolability is enhanced when the FAD cofactor dissociates form enzyme
437725
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
0.005 mM FAD stabilizes enzyme during purification procedure
-
FAD stabilizes
-
methyltetrahydrofolate and S-adenosylmethionine protects enzyme from the loss of FAD after dilution
-
extremely sensitive to proteolysis
-
folate and FAD stabilize the polymorphic mutant enzyme
-
methyltetrahydrofolate and S-adenosylmethionine protects enzyme from the loss of FAD after dilution
-
extremely sensitive to proteolysis
-
inclusion of 10% glycerol during purification is essential for stability
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
oxygen labile, half-life: less than 1 h in aerobic buffer, sodium dithionite prevents inactivation by oxygen
-
437713, 437714
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
on ice, 3 h, loss of about 50% of activity
-
10C, 50 mM Tris-HCl buffer, pH 7.4, 20% glycerol, 2 mM dithionite, in an anaerobic chamber, a few weeks, stable
-
frozen, 50 mM Tris-HCl buffer, pH 7.4, 20% glycerol, 2 mM dithionite, longer time, 10-20% loss of activity
-
-75C, stable for at least 9 months in cell pellets and enzyme extracts
-
-15C, several months, stable
-
-20C, for at least 2 weeks in 10% glycerol
-
-70C, 10% glycerol, several months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
643fold purification of recombinant enzyme, expressed in Saccharomyces cerevisiae
-
about 100fold purification
-
homogeneity
-
purification of wild-type and histidine-tagged D120N and E28Q mutant enzymes
-
recombinant enzyme from strain BL21(DE3)
-
62fold purification of recombinant enzyme, expressed in Sf9 cells from Spodoptera frugiperda
-
homogeneity
-
more than 100fold partial purification
-
20fold purification
-
salting out and DEAE Sepharose column chromatography
-
Toyopearl SuperQ-650M column chromatography and nickel affinity column chromatography
Q5SLG6
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
two MTHFR genes, two cDNAs encoding functional MTHFRs are cloned, sequenced and expressed in Saccharomyces cerevisiae at high levels
-
overexpression of the wild-type enzyme and the chimeric mutant in a Saccharomyces cerevisiae enzyme-deficient strain, complementation of the enzyme-deficient strain, 8fold increased accumulation of S-adenosyl-L-methionine in case of recombinant wild-type expression in yeast, mechanism overview
-
expression of the D120N and E28Q mutant plasmids in Escherichia coli strain AB 1909
-
expression of wild-type and mutant enzymes in Escherichia coli strain AB109 and AB1909-(DE3)7D
-
overexpression in strain BL21(DE3)
-
expressed in Epstein-Barr virus-transformed lymphoblasts
-
expression of recombinant human MTHFR at high levels in Sf9 cells from Spodoptera frugiperda by using a baculovirus expression system
-
wild type and several mutants
-
expressed in Escherichia coli and Neuro-2a cells
-
expressed in HepG2 cells
-
expressed in Mus musculus
-
cloning, disruption and expression of the two genes MET12 and MET13 encoding isoenzymes of MTHFR, MET12 is located on chromosome XVI and encodes a 657 amino acids protein, MET13 is located on chromosome VII, encodes a 599 amino acids protein and is responsible for most of the activity in cell, expression in Escherichia coli BL21
-
expression of chimeric mutant in an enzyme-deficient strain, overexpression of the plant enzyme from Arabidopsis thaliana in an enzyme-deficient strain can complement the mutant and results in 8fold increased accumulation of S-adenosyl-L-methionine, mechanism overview
P53128
enzyme is encoded by the 2 genes met9 and met11, which can complement the double-mutant strain, but they cannot complement for each other in the met9-deficient and met11-mutant, respectively, DNA and amino acid sequence determination and analysis
-
expressed in Escherichia coli BL21(DE3) cells
Q5SLG6
two MTHFR genes, a cDNAs encoding functional MTHFR is cloned, sequenced and expressed in Saccharomyces cerevisiae
Q9SE94
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C181S
-
inactive mutant enzyme
D196G
-
inactive mutant enzyme
E197A
-
mutant enzyme with reduced activity
M182H
-
inactive mutant enzyme
R421ED196G/E197A
-
inactive mutant enzyme
R421K
-
mutant enzyme with reduced activity
A177V
-
mutation does not affect Km or kcat values for NADH or 5,10-methylenetetrahydrofolate
A177V
-
enzyme is thermolabile
A177V
-
enzyme with decreased affinity for its FAD cofactor
A177V
-
crystallization data
A177V
-
the mutation causes loss of the essential cofactor
D120A
-
site-directed mutagenesis, decreased catalytic efficiency in the folate oxidative half-reaction, loss of negative charge near the flavin, small increasing effects on the NADH reductive half reaction
D120K
-
site-directed mutagenesis, decreased catalytic efficiency in the folate oxidative half-reaction, loss of negative charge near the flavin, small increasing effects on the NADH reductive half reaction
D120N
-
mutant with 150fold decreased activity in the physiological NADH-CH2-H4folate oxidoreductase reaction, enzyme is reduced by NADH 30% more rapidly than the wild-type enzyme, it binds methylenetetrahydrofolate in its ring-closed form, but no conversion to the 5-iminium cation, enzyme-bound FAD is more easily reduced and more difficult reoxidized than FAD of wild-type enzyme
D120N
-
site-directed mutagenesis, decreased catalytic efficiency in the folate oxidative half-reaction, loss of negative charge near the flavin, small increasing effects on the NADH reductive half reaction
D120S
-
site-directed mutagenesis, decreased catalytic efficiency in the folate oxidative half-reaction, loss of negative charge near the flavin, small increasing effects on the NADH reductive half reaction
D120V
-
site-directed mutagenesis, decreased catalytic efficiency in the folate oxidative half-reaction, loss of negative charge near the flavin, small increasing effects on the NADH reductive half reaction
E28Q
-
mutant enzyme is unable to catalyze reduction of methylenetetrahydrofolate and is inactive in the physiological NADH-CH2-H4folate oxidoreductase reaction, it binds methyltetrahydrofolate, but reduces not the FAD cofactor, 240fold decrease in NADH-menadione oxidoreductase activity
E28Q
-
crystallization data
F223A
-
mutation impairs both NADH and methylenetetrahydrofolate binding each 40fold and slows catalysis of both half-reactins less than 2fold
F223L
-
affinity for methylenetetrahydrofolate is unaffeacted. Mutant catalyzes the oxidative half-reaction 3fold faster than wild-type
A1298C
-
high level of enzyme activity, retains 40% of its activity after 20 min at 55C
A1298C
P42898
decreased enzyme activity
A1298C
-
MTHFR C677T/C677T and A1298C/A1298C, but not factor V-Leiden, genotypes are associated with stroke. The C677T but not A1298C MTHFR mutation is associated with elevated homocysteine levels in patients and control subjects
A1298C
-
natural polymorphism. Mutation is not associated with increased toxicity of methotrexate
A1298C
-
natural polymorphism, not associated with colorectal cancer risk. Patients with 1298CC and AC genotypes exhibit worse survival than those with the wild-type genotype. Variant C allele of A1298C affects negatively the response to 5-fluorouracil-based chemotherapy
A222V
-
most frequent genetic cause of mild hyperhomocysteinemia, enzyme with enhanced propensity to dissociate into monomers and to lose its FAD cofactor on dilution, increased thermolability of enzyme activity
A222V
-
common polymorphism of enzyme leading to thermolability of protein and mild elevation of plasma homocysteine thrombotic levels
A222V
-
mutant with reduced enzymatic activity, predicts serum folate and plasma homocysteine levels and is useful for predicting toxicity from capecitabine in patients with advanced colorectal cancer
A222V
-
mutant with reduced specific enzyme activity
A222V
-
no correlation can be proved between mutation, patient tumor site, presence of metastasis, and local tumor relapse, the polymorphism is not important in an individual's susceptibility to osteosarcoma and chondrosarcoma in Turkey and may not be a useful marker for identifying patients at high risk of developing sarcomas
A222V
-
the major genetic impact on total plasma homocysteine concentrations is attributable to the MTHFR mutation A222V
A222V
-
the muattion leads to elevated total homocysteine concentration and reduced folate and vitamin B12 levels, but is not associated with the development of bipolar disorders
A222V
-
the mutation corresponding to gene polymorphism C677T is associated with an increased risk of breast and ovarian cancer
A222V
-
the mutation is a risk factor for survival in glioblastoma multiforme
A222V
-
the mutation is not associated with occlusive artery disease and deep venous thrombosis in Macedonians
A677V
-
the mutation is accompanied by hyperhomocysteinemia and protein C deficiency
C1129T
-
natural polymorphism, results in deficiency for enzyme activity
C1141T
-
high level of enzyme activity, retains 40% of its activity after 20 min at 55C
C667T
-
mutant enzyme is more thermolabile than wild type enzyme
C667T
-
high level of enzyme activity, loses almost all its activity after 20 min at 55C, enzyme in patients with TT or TC genotype are more thermolabile than wild type enzyme at 46C
C677T
-
MTHFR C677T/C677T and A1298C/A1298C, but not factor V-Leiden, genotypes are associated with stroke. The C677T but not A1298C MTHFR mutation is associated with elevated homocysteine levels in patients and control subjects
C677T
-
natural polymorphism. Homozygosity for the C677T variant presents a 3fold increased risk of colorectal cancer
C677T
-
natural polymorphism. Mutation is associated with increased toxicity of methotrexate
C677T
-
no significant association between Mthfr mutation C677T and bipolar disorder
C677T
-
seventy-one percent of patients with macrovascular disorders have the MTHFR polymorphism
C677T
-
natural polymorphism, has protective effect on colorectal cancer, the TT genotype showing an odds ratios of 0.06 and the CT of 0.51. C677T genotypes do not affect patient survival. C677T allele carriers respond better to 5-fluorouracil-based chemotherapy than patients with the wild-type CC genotype
E429A
-
A1298C mutation of the MTHRF gene, enzyme with indistinguishable properties from the wild-type
E429A
-
mutant with reduced enzymatic activity, predicts serum folate and plasma homocysteine levels and is useful for predicting toxicity from capecitabine in patients with advanced colorectal cancer
E429A
-
the mutation corresponding to gene polymorphism A1298T is associated with an increased risk of breast cancer
E429A
-
the mutation has a minor elevating effect on total plasma homocysteine concentration
E429A
-
the mutation is not associated with occlusive artery disease and deep venous thrombosis in Macedonians
E429D
-
the muattion leads to elevated total homocysteine concentration and reduced folate and vitamin B12 levels, but is not associated with the development of bipolar disorders
G164C
-
reduced enzyme activity
G458T
-
reduced enzyme activity
R377C
-
the mutation increases plasma homocysteine thiolactone levels 59fold
T34A
-
complete blocking of phosphorylation of enzyme. Mutant enzyme is more active than wild-type and less sensitive to inhibition by S-adenosylmethionie
A222V
Q5SLG6
the mutant shows enhanced instability upon loss of FAD
additional information
-
construction of a chimeric enzyme comprising the yeast N-terminal domain and the Arabidopsis thaliana C-terminal domain, recombinant expression in and complementation of an enzyme-deficient mutant strain with altered sensitivity to S-adenosyl-L-methionine and altered cofactor specifcity
I225V
-
natural polymorphism. Mutation results in an unusual melting curve peak at 53.4C instead of 51.6C or 60.4C in melting curve analysis after real-time polymerase chain reaction
additional information
-
C677T mutation in the coding region of the gene, which replaces a conserved alanine by valine residue in enzyme with reduced activity, increased risk for cardiovascular disease, homozygosity results in a thermolabile enzyme and homocysteinaemia
additional information
-
C677T mutation in MTHFR gene is a polymorphism which leads to the substitution of Ala-222 by valine, A1298C mutation of the MTHFR gene, which leads to the substitution of Glu-429 by alanine
additional information
-
C677T mutation of the gene for methylenetetrahydrofolate reductase: thermolabile enzyme with reduced activity, due to the loss of its riboflavin cofactor, homozygous genotype TT is associated with an increase in plasma total homocysteine, 12% of the healthy white population with this polymorphism
additional information
-
homozygous C677T mutation in the MTHFR gene, resulting in a conserved amino acid change from alanine to valine: enzyme with reduced activity and higher thermolability, elevated plasma homocysteine concentrations, but no genetic risk factor for deep-vein thrombosis, irrespective of factor V Leiden genotype
additional information
-
C677T nucleotide polymorphism, thermolabile, homozygotic persons show hyperhomocysteinemia, the homocysteine level can be reduced by riboflavin supplementation which might be useful in therapy of hyperhomocysteinemia, the mutantion affects the vitamin metabolism
additional information
-
C677T and A1298C gene polymorphisms are associated with reduced enzyme activity, thereby making MTHFR polymorphisms a potential candidate as a cancer-predisposing factor, they may be associated with the individual susceptibility to develop diffuse large B cell lymphoma
additional information
-
C677T and A1298C MTHFR polymorphic variants are associated with the risk of Down syndrome in infants
additional information
-
existence of a joint effect between the MTHFR gene polymorphisms C677T and A1298C on the risk of gastric carcinoma, the single nucleotide polymorphisms are associated with the risk of gastric carcinoma in the east China population
additional information
-
gastric cancer risk is associated with C677T bit not A1298C gene polymorphism
additional information
-
gene polymorphism A1298T is associated with several diseases, such as cardiovascular and psychiatric diseases, neural tube defects, diabetes, and cancer
additional information
-
gene polymorphism C677T does not affect the risk for acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation
additional information
-
gene polymorphism C677T is responsible for thermolabile MTHFR with reduced enzymatic activity and is associated with Alzheimer's disease
additional information
-
genotypes MTHFR C677T and A1298C do not appear to be important risk factors for thromboembolic disorders
additional information
-
genotyping the MTHFR C677T and A1298T gene polymorphism play no role in the prediction of the disease-free survival of patients undergoing adjuvant 5-fluorouracil/methotrexate based chemotherapy against breast cancer
additional information
-
high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes in Iranian colorectal cancer patients
additional information
-
homo- and heterozygous MTHFR gene polymorphisms C677T and A1298C cause elevated plasma homocysteine concentrations after nitric oxide anesthesia
additional information
-
homocysteine levels in children and adolescents are associated with the MTHFR polymorphism C677T genotype
additional information
-
homozygocity for the C677T gene mutation of MTHFR is independently associated with the development of premature with premature myocardial infarction and normal coronary arteries
additional information
-
hyperhomocysteinemia is significantly related to the severity of coronary artery disease independent on MTHFR polymorphism C677T
additional information
-
in patients with acute myocardial infarction, MTHFR 677TT homozygosis is independently associated with a persistently occluded infarct-related artery after thrombolysis
additional information
-
increased MTHFR 677T allele load confers risk for negative symptoms in schizophrenia, while reducing severity of positive symptoms, the biochemical interaction of low serum folate with 677T-variant MTHFR may induce downstream effects salient to the expression of negative symptoms
additional information
-
individuals with a homozygous variant of the MTHFR C677T polymorphism have a reduced risk of colorectal cancer
additional information
-
MTHFR C677T and A1298C gene polymorphisms result in hyperhomocysteinemia which causes abnormal hepatic steatosis
additional information
-
MTHFR C677T and A1298C gene variants play a critical role in NHL outcome, possibly by interfering with the action of methotrexate with significant effects on toxicity and survival in non-Hodgkin's lymphoma patients
additional information
-
MTHFR C677T gene polymorphism leads to a thermolabile enzyme, mild hyperhomocysteinemia, and increased coronary artery disease risk, in Caucasian Brazilians the frequency of the 677T homozygous genotype is increased in coronary artery disease cases in males but not in females, in African Brazilians the mutation is not associated with coronary artery disease in either sex
additional information
-
MTHFR gene polymorphism A1298C is associated with an increased risk for acute lymphoblastic leukemia in Filipino children
additional information
-
MTHFR gene polymorphism C667T interacts with elevated total homocysteine levels leading to an increased risk of ischemic stroke
additional information
-
MTHFR gene polymorphism C677T affects follicular estradiol synthesis
additional information
-
MTHFR gene polymorphism C677T has significantly greater carotid intima-media thickness, higher homocysteine levels, and lower folic acid levels
additional information
-
MTHFR gene polymorphism C677T is a genetic marker for identifying women at increased risk of small for gestational age infants
additional information
-
MTHFR gene polymorphism C677T is a strong modifier of folate status
additional information
-
MTHFR gene polymorphism C677T is associated with idiopathic membranous glomerulonephritis
additional information
-
MTHFR gene polymorphism C677T is neither a determinant of baseline coronary flow indices nor does it modulate the effect of pravastatin on coronary reactivity
additional information
-
MTHFR gene polymorphism C677T modulates an individual's susceptibility to gastric cancer while no association is obeserved for the effect of the MTHFR gene polymorphism A1298C
additional information
-
MTHFR gene polymorphism C677T, but not A1298C has significant association with atlantoaxial dislocation
additional information
-
MTHFR gene polymorphisms A1298C and C677T lead to increased homocysteine plasma levels
additional information
-
MTHFR gene polymorphisms C677T and A1298C do not play a role for the pathogenesis of primary open-angle glaucoma
additional information
-
MTHFR gene polymorphisms C677T and A1298C in combination with angiotensin-converting enzyme insertion/deletion are risk factors for chronic allograft dysfunction
additional information
-
MTHFR genotypes are not associated with cognitive function, cognitive decline, or survival among nonagenarians
additional information
-
MTHFR polymorphisms C677T and A1298T are associated with colorectal cancer
additional information
-
neither the homozygote mutant form nor the heterozygote form of the gene polymorphisms C677T and A1298C is associated with placental abruption
additional information
-
no association between MTHFR C677T gene polymorphism and breast cancer in the Turkish popullation
additional information
-
no association between the maternal 1298C allele, the 677CT/1298AC genotype or any of the corresponding genotypes, and anencephaly
additional information
-
no association is observed between the C677T MTHFR gene polymorphism and the clinical outcome of patients treated with hematopoietic cell transplant
additional information
-
no association with the 5,10-methylenetetrahydrofolate reductase gene polymorphism C677T and major depressive disorder, gene polymorphism C677T results in the production of a mildly dysfunctional thermolabile enzyme and is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations
additional information
-
no associations between the putative functional MTHFR gene polymorphisms, C677T and A1298C, and schizophrenia or bipolar disorder
additional information
-
no correlatio between MTHFR gene polymorphisms C677T and A1298C and serum methotrextae levels in patients with rheumatoid arthritis
additional information
-
no evidence for transmission of the MTHFR 677T allele of gene polymorphism C677T associated with schizophrenia risk
additional information
-
no significant correlation is demonstrated for C677T MTHFR gene polymorphism and homocysteine levels in Brazilian patients with coronary arterial disease, ischemic stroke, and peripheral arterial obstructive disease
additional information
-
no statistically significant differences are seen between the allelic and genotypic distribution of the MTHFR polymorphism C677T in patients chronic allograft nephropathy and with normal renal function
additional information
-
positive association between the MTHFR variant homozygous allele 677TT and breast cancer risk
additional information
-
serum folate concentration is lower in individuals with the MTHFR 677TT genotype than in those with the MTHFR 677CC or 677CT genotypes
additional information
-
the A1298C polymorphism in MTHFR gene has effects on enzyme activity but it can not be considered a major risk factor for coronary artery disease in a selected Iranian population
additional information
-
the association of homocysteine with cardiovascular disease is not modified by MTHFR C677T gene polymorphism
additional information
-
the C1129T gene polymorphism leads to severe MTHFR deficiency which is associated with brain disease
additional information
-
the C667T and A1298C MTHFR gene polymorphisms are not contributing to the aetiology of idiopathic mental retardation in an Indian population
additional information
-
the C677T gene polymorphism causes a valine-to-alanine substitution which produces a thermolabile variant of the enzyme and is associated with higher levels of plasma total homocysteine and congitive test performance in older women
additional information
-
the C677T gene polymorphism decreases enzyme activity and does not significantly contribute to the inherited genetic susceptibility to breast and prostate cancer, while there is some evidence for possible genetic contribution of this polymorphism to the development of head and neck carcinoma
additional information
-
the C677T gene polymorphism does not influence the first and second trimester uterine artery Doppler flow
additional information
-
the C677T gene polymorphism in combination with catechol-O-methyltransferase G324A (Val108/158Met) polymorphism might increase schizophrenia susceptibility
additional information
-
the C677T gene polymorphism is a modulator of a B vitamin network with major effects on homocysteine metabolism und related to the plasma total homocysteine level
additional information
-
the C677T gene polymorphism is associated with hypertension in Caucasian and Asian populations
additional information
-
the C677T gene polymorphism is associated with increased homocysteine and decreased folate concentrations
additional information
-
the C677T gene polymorphism is associated with increased risk of gastric cancer susceptibility in Chinese populations, there is no association between gastric cancer risk and A1298C polymorphism
additional information
-
the C677T gene polymorphism is not associated with obesity
additional information
-
the C677T gene polymorphism is not associated with the risk to develop dyskinesia, motor fluctuation, and psychosis induced by levodopa in Parkinson's disease patients
additional information
-
the C677T MTHFR gene polymorphism contributes to certain executive function deficits in schizophrenia
additional information
-
the C677T MTHFR gene polymorphism is no important risk factor for thromboembolic stroke associated with atrial fibrillation
additional information
-
the C677T MTHFR gene polymorphism is not associated with chronic plaque psoriasis among Caucasians
additional information
-
the C677T MTHFR gene polymorphism results in lower activity of the enzyme and in a subsequent increase in homocysteine levels, is not an independnet predictor on medium-term prognosis after acute coronary syndromes
additional information
-
the C677T polymorphism modifies the age at onset of colorectal cancer in Caucasian Lynch syndrome subjects with the 677T allele having a protective effect, while there is no association between the MTHFR A1298C polymorphism and age at onset of colorectal cancer
additional information
-
the C677T/A1298C compound heterozygous MTHFR genotype is associated with branch retinal artery occlusion
additional information
-
the common MTHFR C677T gene polymorphism causing an Ala to Val protein change is associated with reduced enzyme activity thereby increasing plasma homocysteine level, C667Tis no contributing factor to thrombosis during cancer treatment
additional information
-
the coronary artery disease risk increase is mainly associated with mild hyperhomocysteinaemia in homozygous gene polymorphism C677T, whereas in heterozygous C677T it is mainly associated with the conventional risk factors
additional information
-
the disorders of folate metabolism caused by MTHFR gene polymorphisms C677T and A1298C may lead to several disease states including coronary heart disease, venous thrombosis, and several types of cancer
additional information
-
the effect of MTHFR polymorphisms C677T and A1298C on the risk of lung cancer is undetectable
additional information
-
the G1793A gene polymorphism has a lowering effect on total plasma homocysteine
additional information
-
the genetic risk for gall bladder cancer is not modulated by MTHFR C677T gene polymorphism
additional information
-
the homozygous C677T MTHFR gene polymorphism is associated with coronary artery obstruction
additional information
-
the homozygous mutation (677TT) of the gene polymorphism C677T reduces enzyme activity, alters cellular folate composition, and decreases S-adenosyl methionine synthesis via folate-dependent re-methylation
additional information
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the MTHFR 677 T allele seems to protect against chronic hepatitis B virus infection in young African adults
additional information
-
the MTHFR C677T and A1298C gene polymorphisms are no signifikant risk factors in adult acute lympohoblastic leukemia in the Korean population
additional information
-
the MTHFR C677T gene polymorphism in combination with the thymidylate synthase enhancer region 2R(+) genotype is a risk factor of cholangiocarcinoma in a Korean population
additional information
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the MTHFR C677T gene polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C
additional information
-
the MTHFR C677T genotype is the dominant determinant of nonmethylfolate accumulation in red blood cells
additional information
-
the MTHFR C677T polymorphism is associated with primary closed-angle glaucoma but not primary open-angle glaucoma in patients of Pakistani origin
additional information
-
the MTHFR C677T variant CT and CT + TT genotypes decrease cervix cancer risk in North Indian women
additional information
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the MTHFR gene polymorphism C677T has no contribution in hyperhomocysteinemia in epileptic patients receiving carbamazepine or valproic acid
additional information
-
the MTHFR gene polymorphism C677T is associated with diffuse multicystic encephalomalacia
additional information
-
the MTHFR gene polymorphism C677T is associated with impaired catalytic properties of the enzyme, betaine is a strong determinant of plasma tHcy in subjects with low serum folate and homozygous C677T genotype
additional information
-
the MTHFR gene polymorphism C677T is associated with lumbar spine and hip bone mineral density in children
additional information
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the MTHFR gene polymorphism C677T is no risk factor for the progression of fatty liver disease to nonalcoholic steatohepatitis
additional information
-
the MTHFR gene polymorphism C677T is not associated with congenital heart disease and may be linked to the development of aortic arch anomalies
additional information
-
the MTHFR gene polymorphism C677T is not associated with the development of diabetic nephropathy in Turkish type 2 diabetic patients
additional information
-
the MTHFR gene polymorphisms C677T and A1298C are associated with altered enzyme activity
additional information
-
the presence of the T allele in the C677T MTHFR gene polymorphism is associated with higher homocysteine levels, which is more prominent in men than in women
additional information
-
the simultaneous presence of C677T and A1298A genotypes provides a significant risk of developing coronary artery disease, while the A1298C genotype combined with C677C shows a significant trend towards a decrease in coroary artery disease occurrence
additional information
-
the T allele of the MTHFR C677T genotype is significantly associated with atherothrombotic infarction
additional information
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there is a correlation between MTHFR C677T gene mutations and recurrent fetal loss
additional information
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there is a trend for a higher MTHFR 677T allele frequency in breast cancer cases than in controls
additional information
-
there is some evidence of association between MTHFR C677T gene polymorphism and diabetic nephropathy
additional information
-
analysis of two mutations in MTHFR gene in compound heterozygous patients with extremely low or undetectable enzyme activity. Mutation c.523G>A leads to an Ala>Thr transition in the catalytic domain of the enzyme, mutation c.1166G>A induces alternative splicing of exon 7 at the junction of the catalytic and regulatory domains. Both parents carry only one of these mutations and present with moderate and intermediate hyperhomocysteinemia, respectively, without neurological symptoms
additional information
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a C677T polymorphism is associated with an increased risk for the development of cardiovascular disease, Alzheimers disease, and depression in adults and of neural tube defects in the fetus
T980C
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reduced enzyme activity
additional information
-
enzyme null mutants lack 5-methyltetrahydrofolate and cannot utilize exogenous homocysteine for growth. In mouse model of infection, null mutants show good infectivity and virulence
R377C
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the mutation increases plasma homocysteine thiolactone levels 59fold
additional information
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mutant strain RRY1 with single disruption of MET13 and strain RRY3 with double disruption of both MET12 and MET13, but not strain RRY2 with single disruption of MET12, result in loss of MTHFR activity and methionine auxothrophy, they can be complemented by overexpression of the human enzyme, but not by overexpression of the Escherichia coli metF gene
additional information
P53128
construction of a chimeric enzyme comprising the yeast N-terminal domain and the Arabidopsis thaliana C-terminal domain, recombinant expression in and complementation of an enzyme-deficient mutant strain with altered sensitivity to S-adenosyl-L-methionine and altered cofactor specifcity
additional information
Saccharomyces cerevisiae DAY4
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mutant strain RRY1 with single disruption of MET13 and strain RRY3 with double disruption of both MET12 and MET13, but not strain RRY2 with single disruption of MET12, result in loss of MTHFR activity and methionine auxothrophy, they can be complemented by overexpression of the human enzyme, but not by overexpression of the Escherichia coli metF gene
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Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
dissociated enzyme after treatment with 1 M urea, no refolding and renaturation is possible after treatment with 1.2 M NaCl
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
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natural polymorphism I225V results in an unusual melting curve peak at 53.4C instead of 51.6C or 60.4C in melting curve analysis after real-time polymerase chain reaction. Potential ability of melting analysis to identify new sequence variants
medicine
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mutation in gene for methylenetetrahydrofolate reductase is a cause of moderate homocysteinaemia, which is a risk factor for arteriosclerosis and thrombosis, patients with MTHFR deficiency have low methionine concentrations in plasma
medicine
-
methylenetetrahydrofolate reductase deficiency causes homocystinuria
medicine
-
deficiency and thermolability of enzyme as cause of mild homocysteinemia with premature vascular disease
medicine
-
methylenetetrahydrofolate reductase deficiency as cause of homocysteinuria
medicine
-
C677T mution of MTHRF gene is the most frequent genetic cause of mild hyperhomocysteinemia, a risk factor for cardiovascular disease
medicine
-
association of A222V genotype with the Gc2 polymorphism of the vitamin D-binding protein. A222V mutant individuals additionally show a quantitative reduction of apolipoprotein A-I
medicine
-
MTHFR inhibition may be a novel anticancer approach
medicine
-
MTHFR is important for postnatal growth and vitality and 5-methyltetrahydrofolate deficiency contributes to the high postnatal mortality, Mefolinate may be a good candidate drug for treatment of severe MTHFR deficiency
medicine
-
the consequences of a deficient MTHFR genotype are probably dependent on the folate intake status, there is no clear conclusion regarding the influence of MTHFR polymorphisms on 5-fluorouracil-based treatment in colorectal cancer
medicine
-
homozygosity for the C677T natural polymorphism presents a 3fold increased risk of colorectal cancer. Low intake of methyl-donor nutrients is associated with an increased risk of colorectal cancer in homozygous participants for the C677T polymorphism
medicine
-
in Parkinson patients, plasma homocysteine elevation may be caused by levodopa administration, and further promoted by MTHFR C677T heterozygotes and homozygote C677T/C677T, but not by A1298C genotypes. The promoting elevation in 1298A homozygotes is attributed to combining the 677T allele. Neither C677T nor A1298C genotypes contribute to elevating plasma homocysteine in Parkinson patients without levodopa treatment
medicine
-
meta-analysis of Mthfr polymorphisms affecting methotrexate toxicity. Polymorphism C677T is associated with increased toxicity of methotrexate,while polymorphism A1298C is not
medicine
-
MTHFR mutant C677T homozygotes who are also carriers of cystathione beta-synthase 844ins68 polymorphism have homocysteine and folate concentrations similar to those of individuals with the MTHFR heterozygous C677C/C677T and wild-type genotypes. Homocysteine levels in MTHFR double mutant subjects carrying the cystathione beta-synthase 844ins68 allele are 24.1% lower than in non-carriers, and serum folate levels are 27.7% higher. These suggests that the cystathione beta-synthase 844ins68 allele normalizes homocysteine and folate levels in MTHFR C677T/C677T individuals
medicine
-
mutations in the MTHFR gene decrease the onset risk of acute lymphoblastic leukemia with relapse in the setting of no folate supplementation in pregnancy, but not of relapse-free acute lymphoblastic leukemia
medicine
-
No significant difference is found in either Mthfr allele frequencies or genotype distribution between patients with bipolar disorder and controls in an association study in the Chinese population. The meta-analysis result shows no significant association between Mthfr C677T and bipolar disorder
medicine
-
no significant differences in plasma homocysteine levels and MTHFR genotypes are found in patients with systemic sclerosis compared to controls or in systemic sclerosis patients with limited cutaneous compared to diffuse disease. Seventy-one percent of patients with macrovascular disorders have MTHFR polymorphism C677T. In addition, 45% of patients with hyperhomocysteinemia have pulmonary hypertension. The presence of MTHFR C677T mutation influences the incidence of macrovascular abnormalities in SSc patients
medicine
-
plasma homocysteine levels are significantly elevated in patients lacking Mthfr activity or cystathione beta-synthase activity
medicine
-
study on association of factor V-Leiden and methylenetetrahydrofolate reductase C677T and A1298C mutations with stroke. MTHFR C677T/C677T and A1298C/A1298C, but not factor V-Leiden, genotypes are associated with stroke. The C677T but not A1298C MTHFR mutation is associated with elevated homocysteine levels in patients and control subjects. In addition to hypertension, the significant predictors for stroke are MTHFR C677T and C677T/C677T and A1298C/A1298C genotypes, together with hyperhomocysteinemia, indicating a synergistic effect of MTHFR mutations with elevated homocysteine and other risk factors in pathogenesis of stroke
medicine
-
MTHFR variant allele C677T has a protective effect on colorectal cancer development, whereas the variant allele of the A1298C does not produce any effect on disease risk. Both MTHFR polymorphisms are relevant and independent factors of patient outcome after 5-fluorouracil-based treatment of colorectal cancer
nutrition
-
homozygosity for the C677T natural polymorphism presents a 3fold increased risk of colorectal cancer. Low intake of methyl-donor nutrients is associated with an increased risk of colorectal cancer in homozygous participants for the C677T polymorphism
medicine
-
MTHFR deficiency in mice is accompanied with hyperhomocysteinemia and decreased hematocrit, hemoglobin, and red blood cell numbers, increased nephrotoxicity und hepatotoxicity compared to wild type animals
medicine
-
maternal MTHFR and dietary folate deficiencies in Mthfr +/- mice result in increased developmental delays and smaller embryos. Folate-deficient mice also have increased embryonic losses and severe placental defects, including placental abruption and disturbed patterning of placental layers. Folate-deficient placentae have decreased ApoA-I expression, and there is a trend toward a negative correlation between ApoA-I expression with maternal homocysteine concentrations
medicine
-
mice carrying a mutation in the adenomatous polyposis coli gene Apc, a model for intestinal polyposis, fed with high folate diets from weaning develop more adenomas than those fed the folic acid deficient diet or the control diet. Mthfr deficiency does not affect adenoma number. When the folic acid deficient diet and control diet are administered to dams prior to conception, throughout pregnancy and continued in offspring post-weaning, Apc -/+ offspring fed folic acid deficient diet develop fewer adenomas than those fed control diet. Mthfr+/- genotype of the mother or of the offspring also reduces adenoma numbers in the Apc -/+ offspring. Adenoma number is inversely correlated with plasma homocysteine, intestinal dUTP/dTTP ratios, and levels of intestinal apoptosis
nutrition
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mice carrying a mutation in the adenomatous polyposis coli gene Apc, a model for intestinal polyposis, fed with high folate diets from weaning develop more adenomas than those fed the folic acid deficient diet or the control diet. Mthfr deficiency does not affect adenoma number. When the folic acid deficient diet and control diet are administered to dams prior to conception, throughout pregnancy and continued in offspring post-weaning, Apc -/+ offspring fed folic acid deficient diet develop fewer adenomas than those fed control diet. Mthfr+/- genotype of the mother or of the offspring also reduces adenoma numbers in the Apc -/+ offspring. Adenoma number is inversely correlated with plasma homocysteine, intestinal dUTP/dTTP ratios, and levels of intestinal apoptosis