1.5.1.20: methylenetetrahydrofolate reductase [NAD(P)H]
This is an abbreviated version!
For detailed information about methylenetetrahydrofolate reductase [NAD(P)H], go to the full flat file.
Word Map on EC 1.5.1.20
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1.5.1.20
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nitrite
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homocysteine
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medicine
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paracoccus
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assimilatory
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denitrification
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chlorate
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narghi
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resde
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napc
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molybdoenzyme
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pantotrophus
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ammonification
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nutrition
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analysis
- 1.5.1.20
- nitrite
- homocysteine
- medicine
- paracoccus
-
assimilatory
-
denitrification
- chlorate
- narghi
-
resde
- napc
-
molybdoenzyme
- pantotrophus
-
ammonification
- nutrition
- analysis
Reaction
Synonyms
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, AtMTHFR-1, EC 1.1.1.171, EC 1.1.1.68, EC 1.1.99.15, EC 1.7.99.5, HsMTHFR, MET13, methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide) reductase, methylenetetrahydrofolate reductase, methylenetetrahydrofolate reductase (NADPH), methylenetetrahydrofolic acid reductase, MetVF-type methylenetetrahydrofolate reductase, More, MTHFR, MTHFR2, N5,10-methylenetetrahydrofolate reductase, N5,N10-methylenetetrahydrofolate reductase, NADH:CH2-H4folate oxidoreductase, NapAB, reductase, methylenetetrahydrofolate (reduced nicotinamide adenine dinucleotide phosphate), reductase, methylenetetrahydrofolate (reduced riboflavin adenine dinucleotide), respiratory nitrate reductase, type II-MTHFR
ECTree
1.5.1.20 methylenetetrahydrofolate reductase [NAD(P)H]Advanced search results
results (
results (Inhibitors
Inhibitors on EC 1.5.1.20 - methylenetetrahydrofolate reductase [NAD(P)H]
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(+)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate
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inhibits at high concentrations
(S)-SKI-72
binds MTHFR via its allosteric domain with nanomolar affinity. Assay of MTHFR activity in the presence of (S)-SKI-72 demonstrates inhibition of purified enzyme with submicromolar potency and endogenous MTHFR from HEK293 cell lysate in the low micromolar range, both of which are lower than AdoMet. Nevertheless, unlike AdoMet, (S)-SKI-72 is unable to completely abolish MTHFR activity, even at very high concentrations
(S)-SKI-73
a (S)-SKI-72 prodrug derivative, in which the 9'-amine moiety is cloaked with the trimethyl-locked quinone butanoate moiety, on intact HEK293 cells. Once (S)-SKI-73 passes inside the cell membrane, it is metabolised into (S)-SKI-72 and 60-N benzylhomosinefungin, which then accumulates inside the cell
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diethyldicarbonate
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20 mM NADP+ and 20 mM NAD+ partially protected the enzyme against inactivation whereas 20 mM nicotinamide gives complete protection
N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamyl-gamma-glutamyl-gamma-glutamylglutamic acid
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N-(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)-gamma-glutamyl-gamma-glutamylglutamic acid
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N-([5-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2,3-dihydrothiophen-2-yl]carbonyl)-4-methylideneglutamic acid
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N-[4-[2-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]-2-fluorobenzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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N-[4-[2-(2-amino-4-methylquinazolin-6-yl)ethyl]benzoyl]-4-methylideneglutamic acid
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p-chloromercuribenzoate
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60% inhibition of the methylenetetrahydrofolate reductase activity at 0.04 mM, 83% inhibition of the menadione reductase activity at 0.04 mM
dihydrofolate
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competitive with respect to 5,10-methylenetetrahydrofolate and uncompetitive with respect to NADPH
dihydropteroylpolyglutamate
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most potent inhibitor is dihydropteroylhexaglutamate
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S-adenosyl-L-methionine
feed-back regulation of the methyl group biosynthesis pathway in vivo, the chimeric mutant enzyme is insensitive to inhibition by S-adenosyl-L-methionine
S-adenosylmethionine
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inhibition of the enzyme in crude extracts from fresh liver biopsies, but not after purification from cadaver liver
S-adenosylmethionine
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strong, reversible allosteric inhibition, prevented by S-adenosylhomocysteine
S-adenosylmethionine
SAM, allosteric inhibition by the reaction product. MTHFR phosphorylation, identified on 11 N-terminal residues (16 in total), increases sensitivity to SAM binding and inhibition
S-adenosylmethionine
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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
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allosteric inhibition; inhibition partially reversed by S-adenosylhomocysteine
S-adenosylmethionine
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inhibition partially reversed by S-adenosylhomocysteine
S-adenosylmethionine
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effect on equilibrium between active and inactive form of enzyme
S-adenosylmethionine
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inhibits both the reduction of the enzyme-bound flavin by 5-methyltetrahydrofolate and the reoxidation of reduced enzyme by 5,10-methylenetetrahydrofolate
additional information
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no inhibition by S-adenosyl-L-methionine, which is no feed-back regulator of the methyl group biosynthesis pathway in plants
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additional information
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vitamin B12 and methionine can repress enzyme biosynthesis
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additional information
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inhibiting MTHFR with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells
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additional information
the regulatory domain of MTHFR can be targeted by small molecules and presents (S)-SKI-72 as an excellent candidate for development of MTHFR inhibitors, docking study, overview. Phosphorylation of MTHFR, which occurs mainly in the N-terminal serine rich region, further sensitises the protein to this inhibition. Enzyme inhibition may be reversed by the binding of S-adenosylhomocysteine (AdoHcy), the demethylated form of Ado-Met, to the regulatory domain. (S)-SKI-72 exhibits poor membrane permeability
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additional information
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not inhibitory: S-adenosyl-L-methionine, no substrate inhibition up to 0.25 mM
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additional information
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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
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additional information
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residues essential for enzyme activity: arginine, histidine, tryptophan
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additional information
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gene contains a putative S-adenosylmethionione binding sequence, that is inhibitory in eukaryotic MTHFR
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