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(2S,4S)-amino-4,5-epoxypentanoic acid
-
1-(3-(2-ethoxyphenyl)ureidoacetyl)-4-(2-methyl-5-nitrophenyl)semicarbazide
binding to adenosyl region of the active site
1-(4-chloro-2-nitrophenyl)-3-(4-sulfamoylphenyl)-urea
binding to adenosyl region of the active site
1-aminocyclopentanecarboxylic acid
-
-
1-methyluric acid
10 mM, 43.4% inhibition
1-Methylxanthine
10 mM, 35.9% inhibition
2,6-diaminopurine
10 mM, 29.3% inhibition
2,6-dichloropurine
10 mM, 35.5% inhibition
2-amino-6-carboxyethylmercaptopurine
10 mM, 31.9% inhibition
2-amino-6-chloropurine riboside
10 mM, 17.2% inhibition
2-amino-6-chloropurine-9-acetic acid
10 mM, 23.5% inhibition
2-Aminopurine
10 mM, 11.0% inhibition
2-Hydroxypurine
10 mM, 33.8% inhibition
3,7-dimethyluric acid
10 mM, 27.9% inhibition
3-morpholinosydnoniimide
-
loss of liver MAT activity in vivo
5-amino-L-norvaline
10-25% inhibition with 5 mM; 10-25% inhibition with 5 mM; 10-25% inhibition with 5 mM
5-azacytidine
-
0.2 mM leads to significant reduction of AdoMetS protein expression
6-benzyloxypurine
10 mM, 17.7% inhibition
6-bromopurine
10 mM, 31.4% inhibition
6-Chloropurine
10 mM, 31.4% inhibition
6-Chloropurine riboside
10 mM, 17.1% inhibition
6-Cyanopurine
10 mM, 24.2% inhibition
6-dimethylallylaminopurine riboside
10 mM, 41.6% inhibition
6-Dimethylaminopurine
10 mM, 28.0% inhibition
6-Mercaptopurine
10 mM, 40.1% inhibition
6-mercaptopurine riboside
10 mM, 30.0% inhibition
6-propoxypurine
10 mM, 27.9% inhibition
7-hydroxypropyl theophylline
10 mM, 16.1% inhibition
7-Methyluric acid
10 mM, 11.4% inhibition
7-methylxanthine
10 mM, 36.3% inhibition
8-aza-2,6-diaminopurine
10 mM, 40.0% inhibition
8-Azaguanine
10 mM, 81.7% inhibition
8-chlorotheophylline
10 mM, 7.0% inhibition
Adenyl-5'-ylimidodiphosphate
-
competitive with ATP
ADP
35-50% inhibition with 5 mM; 35-50% inhibition with 5 mM; 35-50% inhibition with 5 mM
alpha,beta-methylene-adenosine tetraphosphate
-
-
alpha,beta-methylene-ATP
-
-
alpha-methyl-DL-methionine
10 mM, 18.8% inhibition
AMP
causes complete inactivation of the enzyme
Azathioprine
10 mM, 75.5% inhibition
Ba2+
70.70% residual activity at 5 mM
bacterial lipopolysaccharide
-
beta,gamma-methylene-ATP
-
-
Br-
93.33% residual activity at 5 mM
carbon tetrachloride
-
depletion of glutathione levels reduces MAT I/III activities in vivo
CH3COO-
92.25% residual activity at 5 mM
Cl-
85.27% residual activity at 5 mM
Co2+
-
about 45% residual activity at 10 mM
diimidotriphosphate
mechanism
DL-2-Amino-trans-4-hexenoic acid
-
-
ethanol
25 mM ethanol substantially decreases the enzymatic activity of MAT II
Ethionine
32-38% inhibition with 5 mM; 32-38% inhibition with 5 mM; 32-38% inhibition with 5 mM
F-
88.84% residual activity at 5 mM
fluorinated N,N-dialkylaminostilbene-5
-
i.e. FIDAS
-
Fumarylacetoacetate
-
reduces MAT I/III activity
glycerol
-
inhibits kidney isoenzyme gamma
GSH
causes complete inactivation of the enzyme
I-
87.91% residual activity at 5 mM
L-2-Amino-4-hexynoic acid
-
-
L-2-Amino-4-methoxy-cis-but-3-enoic acid
L-2-Amino-4-methylthio-cis-but-3-enoic acid
-
-
L-buthionine-(S,R)-sulfoximine
L-ethioninamide
10 mM, 23.9% inhibition
L-methionine methyl ester
10 mM, 17.7% inhibition
L-methionine sulfone
10 mM, 9.2% inhibition
L-methionine sulfoxide
10 mM, 4.0% inhibition
L-methionine sulfoximine
10 mM, 12.6% inhibition
L-Penicillamine
10 mM, 15.0% inhibition
Li+
81.40% residual activity at 5 mM
methanol
2.4% methanol depresses methionine adenosyltransferase specific activity, this effect is not observed with 0.8% methanol
methylthio propionaldehyde
10 mM, 18.4% inhibition
Mg2+
-
inhibitory above 8.5 mM
N-ethylmaleimide
time-dependent inactivation of both MAT activities
Ni2+
-
about 1% residual activity at 10 mM
nitrosoglutathione
-
reversibly inhibits the isozyme MAT1 via NO binding to Cys114, no inhibition of isozymes MAT2 and MAT3, molecular mechanism for S-nitrosylation of the enzyme
NO
the enzyme is inhibited upon S-nitrosylation. S-Nitrosylation of the enzyme is mediated via several cysteine residues, including Cys52, Cys113 and Cys187. Nitrosylation is a reversible posttranslational modification upon nitrosative stress
O-methylguanine
10 mM, 60.3% inhibition
putrescine
15-25% inhibition with 5 mM; 15-25% inhibition with 5 mM; 15-25% inhibition with 5 mM
S-adenosyl-L-ethionine
-
-
S-adenosyl-L-homocysteine
S-carbamylcysteine
-
competitive with methionine
S-nitrosoglutathione monoethyl ester
-
inactivates
S-nitrosylated glutathione
-
rapid and dose-dependent loss of enzymatic activity of MAT I/III
S-Trifluoromethyl-L-homocysteine
-
-
SIN-1
-
rapid and dose-dependent loss of enzymatic activity of MAT I/III
spermidine
15-34% inhibition with 5 mM; 15-34% inhibition with 5 mM; 15-34% inhibition with 5 mM
spermine
30-40% inhibition with 5 mM; 30-40% inhibition with 5 mM; 30-40% inhibition with 5 mM
uric acid
10 mM, 45.6% inhibition
xanthine
10 mM, 35.4% inhibition
ATP
-
-
ATP
-
ATP and methionine act as a switch between two different MAT III isoforms
ATP
causes complete inactivation of the enzyme
bacterial lipopolysaccharide
-
decreases MAT activity in vivo
-
bacterial lipopolysaccharide
-
results in the accumulation of nitrites and nitrates in serum and in the inactivation of MAT I/III
-
Ca2+
-
about 5% residual activity at 10 mM
Ca2+
86.36% residual activity at 5 mM
CTP
60-70% inhibition with 5 mM; 60-70% inhibition with 5 mM; 60-70% inhibition with 5 mM
CTP
-
20 mM, 37% inhibition, S-adenosylmethionine synthetase B; 20 mM, 40% inhibition, S-adenosylmethionine synthetase A
Cu2+
-
complete inhibition at 10 mM
Cu2+
isozyme subunit MATalpha2 is inhibited by 0.25 mM Cu2+ in the presence or absence of dithiothreitol, strong reduction in MAT2B gene expression induced by Cu2+ (60%), copper effects can only be prevented by buthionine sulfoximine, whereas N-acetylcysteine and neocuproine are ineffective
Cu2+
25.74% residual activity at 5 mM
cycloleucine
-
competitive
cycloleucine
1-aminocyclopentane-1-carboxylic acid, specific MAT inhibitor
cycloleucine
10 mM, 25.8% inhibition
cycloleucine
-
25 mM, 56% inhibition, S-adenosylmethionine synthetase A; inhibits only at sub saturating concentrations of methionine
Dimethylsulfoxide
-
-
Dimethylsulfoxide
-
weak inhibition of liver isoenzyme
Dimethylsulfoxide
-
slight inhibition of gamma isoenzyme from kidney
diphosphate
-
-
diphosphate
-
inhibition for S-adenosylmethionine and L-methonine
diphosphate
-
individually a weak inhibitor, in combination with phosphate there is a marked synergistic effect
diphosphate
-
inhibits high-MW isoenzyme, no effect on low-MW enzyme
diphosphate
-
20 mM, 30% inhibition, S-adenosylmethionine synthetase A; 20 mM, 49% inhibition, S-adenosylmethionine synthetase B
Fe2+
-
about 15% residual activity at 10 mM
Fe2+
59.22% residual activity at 5 mM
GTP
not accepted as a substrate but inhibits the reaction in the presence of ATP, 70-80% inhibition with 5 mM; not accepted as a substrate but inhibits the reaction in the presence of ATP, 70-80% inhibition with 5 mM; not accepted as a substrate but inhibits the reaction in the presence of ATP, 70-80% inhibition with 5 mM
GTP
-
competitive with respect to ATP and noncompetitive with L-methionine
GTP
-
20 mM, 50% inhibition, S-adenosylmethionine synthetase B; 20 mM, 56% inhibition, S-adenosylmethionine synthetase A
hydrogen peroxide
-
reduces MAT I/III activity
hydrogen peroxide
-
inactives CHO cells-MAT, prevented by desferoxamine. Time- and dose-dependent inactivation of MAT I/III, activity recovered by addition of glutathione
K+
-
-
K+
85.27% residual activity at 5 mM
L-2-Amino-4-methoxy-cis-but-3-enoic acid
-
-
L-2-Amino-4-methoxy-cis-but-3-enoic acid
-
-
L-buthionine-(S,R)-sulfoximine
-
inhibits glutathione synthesis and this decreases MAT activity in vivo. Prevented by the administration of glutathione-ethyl ester
L-buthionine-(S,R)-sulfoximine
-
inactivates hepatic MAT, prevented by the administration of glutathione-ethyl ester
L-ethionine
-
1.2 mM leads to significant reduction of AdoMetS protein expression
L-ethionine
-
competitive with respect to methionine for S-adenosylmethionine formation and noncompetitive with respect to ATP
L-ethionine
10 mM, 20.4% inhibition
L-methionine
-
-
L-methionine
-
ATP and methionine act as a switch between two different MAT III isoforms
L-methionine
30% reduction in total activity is detected at 5 mM L-methionine; 30% reduction in total activity is detected at 5 mM L-methionine; 30% reduction in total activity is detected at 5 mM L-methionine
methylthioadenosine
-
lowers expression of MAT2A and MAT2beta
methylthioadenosine
1 mM downregulates MAT2A expression
Mn2+
-
about 80% residual activity at 10 mM
Mn2+
73.49% residual activity at 5 mM
Mn2+
-
inhibition in presence of Mg2+
Na+
80.16% residual activity at 5 mM
Na+
-
in presence of Mg2+
nitric oxide
-
two MAT III isoforms, one with low tripolyphosphatase activity that is insensitive to NO and another with high tripolyphosphatase activity that is inhibited by NO
nitric oxide
-
inactivates hepatic MAT
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
reduces MAT I/III activity
p-chloromercuribenzoate
-
alpha and beta isoenzymes completely inhibited, gamma isoenzyme slightly inhibited
phosphate
-
-
phosphate
-
competitive toward both ATP and methionine
phosphate
-
individually a weak inhibitor, in combination with diphosphate there is a synergistic inhibitory effect
phosphate
-
10 mM, 19% inhibition, S-adenosylmethionine synthetase B; 10 mM, 45% inhibition, S-adenosylmethionine synthetase A
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
not inhibitory
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-methionine
-
product inhibition. Compared with the wild-type MAT, as little as 200 mM sodium p-toluenesulfonate is required to completely overcome the product inhibition of I303V mutant enzyme on a 30 mM scale incubation
S-adenosyl-L-methionine
product inhibition
S-adenosyl-L-methionine
-
feedback inhibition of isozyme MAT II
S-adenosylmethionine
-
-
S-adenosylmethionine
-
non competitive with ATP at low methionine concentration
S-adenosylmethionine
-
lowers expression of MAT2A and MAT2beta
S-adenosylmethionine
non competitive inhibition
S-adenosylmethionine
-
more than 50% inhibition at 1 mM
S-adenosylmethionine
-
noncompetitive inhibitor with respect to ATP and methionine
S-adenosylmethionine
5 mM downregulates MAT2A expression
S-adenosylmethionine
-
inhibition of rat kidney enzyme and rat liver MAT-II, weak inhibition of rat liver MAT-I
S-adenosylmethionine
-
above 0.3 mM inhibits both high-MW and low-MW isoenzymes
S-adenosylmethionine
-
inhibits the A form but not the B form; non-competitive, S-adenosylmethionine synthetase A; slight inhibition of S-adenosylmethionine synthetase B
S-nitrosoglutathione
the enzyme is inhibited upon S-nitrosylation. S-Nitrosylation of the enzyme is not only mediated via a single cysteine but via several cysteine residues, including Cys52, Cys113 and Cys187
S-nitrosoglutathione
-
inhibits S-adenosylmethionine sinthetase activity
S-nitrosoglutathione
-
inactivates MATI/III by 70%
Tetrapolyphosphate
-
10 mM, 40% inhibition, S-adenosylmethionine synthetase B; 10 mM, 50% inhibition, S-adenosylmethionine synthetase A
tripolyphosphate
-
-
tripolyphosphate
strong inhibitor; strong inhibitor; strong inhibitor
tripolyphosphate
-
competitive with ATP
tripolyphosphate
-
competitive with ATP and non competitive with L-methionine
tripolyphosphate
-
competitive with ATP; non competitive with L-methionine
tripolyphosphate
-
activation or inhibition, depending on isoenzyme, S-adenosylmethionine and tripolyphosphate concentration
tripolyphosphate
-
1.0 mM, 57% inhibition, S-adenosylmethionine synthetase A; 1.0 mM, 62% inhibition, S-adenosylmethionine synthetase B
UTP
-
-
Zn2+
-
about 10% residual activity at 10 mM
Zn2+
22.17% residual activity at 5 mM
additional information
addition of reducing agents has no effect; addition of reducing agents has no effect; addition of reducing agents has no effect
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additional information
addition of reducing agents has no effect; addition of reducing agents has no effect; addition of reducing agents has no effect
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additional information
addition of reducing agents has no effect; addition of reducing agents has no effect; addition of reducing agents has no effect
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additional information
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addition of reducing agents has no effect; addition of reducing agents has no effect; addition of reducing agents has no effect
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additional information
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overview of the regulatory properties, effect of L-methionine analogues and influence of L-methionine concentration on activating and inhibiting effects, effect of tripolyphosphate and p-hydroxymercuribenzoate
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additional information
-
reactive oxygen and nitrogen species induce the inactivation of MAT I/III
-
additional information
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no inhibition with cycloleucine, L-homocysteine, L-norleucine, L-cis-2-amino-4-methoxy-3-butenoic acid, S-adenosylhomocysteine, 5'-methylthioadenosine, sinefungin
-
additional information
not inhibitory: (R)-methioninol, 1,3,7-trimethyluric acid, 6-methylpurine
-
additional information
-
not inhibitory: (R)-methioninol, 1,3,7-trimethyluric acid, 6-methylpurine
-
additional information
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MAT is inactivated after 6 h of incubation in hypoxia (3% O2) in rat hepatocytes, prevented by NG-monomethyl-L-arginine methyl ester. Hepatic MAT s a sensible target for free radicals in vivo
-
additional information
-
S-adenosyl(5')-3-methylthiopropylamine does not inhibit
-
additional information
no effect on activity at 0.1 mM Ni2+
-
additional information
-
no effect on activity at 0.1 mM Ni2+
-
additional information
-
overexpression of yeast AdoMet synthase plus cap guanine-N7 methyltransferase affords greater resistance to sinefungin than either enzyme alone
-