2.5.1.6 (2S,4S)-amino-4,5-epoxypentanoic acid - 125163 2.5.1.6 1-(3-(2-ethoxyphenyl)ureidoacetyl)-4-(2-methyl-5-nitrophenyl)semicarbazide binding to adenosyl region of the active site 76514 2.5.1.6 1-(4-chloro-2-nitrophenyl)-3-(4-sulfamoylphenyl)-urea binding to adenosyl region of the active site 76515 2.5.1.6 1-aminocyclopentanecarboxylic acid - 90469 2.5.1.6 1-methyluric acid 10 mM, 43.4% inhibition 23326 2.5.1.6 1-Methylxanthine 10 mM, 35.9% inhibition 5087 2.5.1.6 2,6-diaminopurine 10 mM, 29.3% inhibition 2634 2.5.1.6 2,6-dichloropurine 10 mM, 35.5% inhibition 13382 2.5.1.6 2-amino-6-carboxyethylmercaptopurine 10 mM, 31.9% inhibition 125160 2.5.1.6 2-amino-6-chloropurine riboside 10 mM, 17.2% inhibition 32035 2.5.1.6 2-amino-6-chloropurine-9-acetic acid 10 mM, 23.5% inhibition 125157 2.5.1.6 2-Aminopurine 10 mM, 11.0% inhibition 6419 2.5.1.6 2-Hydroxypurine 10 mM, 33.8% inhibition 12309 2.5.1.6 3,7-dimethyluric acid 10 mM, 27.9% inhibition 23325 2.5.1.6 3-morpholinosydnoniimide loss of liver MAT activity in vivo 112577 2.5.1.6 5-amino-L-norvaline 10-25% inhibition with 5 mM; 10-25% inhibition with 5 mM; 10-25% inhibition with 5 mM 33186 2.5.1.6 5-azacytidine 0.2 mM leads to significant reduction of AdoMetS protein expression 5497 2.5.1.6 6-benzyloxypurine 10 mM, 17.7% inhibition 125158 2.5.1.6 6-bromopurine 10 mM, 31.4% inhibition 31750 2.5.1.6 6-Chloropurine 10 mM, 31.4% inhibition 2823 2.5.1.6 6-Chloropurine riboside 10 mM, 17.1% inhibition 6470 2.5.1.6 6-Cyanopurine 10 mM, 24.2% inhibition 43590 2.5.1.6 6-dimethylallylaminopurine riboside 10 mM, 41.6% inhibition 125162 2.5.1.6 6-Dimethylaminopurine 10 mM, 28.0% inhibition 15587 2.5.1.6 6-Mercaptopurine 10 mM, 40.1% inhibition 1345 2.5.1.6 6-mercaptopurine riboside 10 mM, 30.0% inhibition 7132 2.5.1.6 6-propoxypurine 10 mM, 27.9% inhibition 125161 2.5.1.6 7-hydroxypropyl theophylline 10 mM, 16.1% inhibition 125156 2.5.1.6 7-Methyluric acid 10 mM, 11.4% inhibition 43631 2.5.1.6 7-methylxanthine 10 mM, 36.3% inhibition 2307 2.5.1.6 8-aza-2,6-diaminopurine 10 mM, 40.0% inhibition 13321 2.5.1.6 8-Azaguanine 10 mM, 81.7% inhibition 2075 2.5.1.6 8-chlorotheophylline 10 mM, 7.0% inhibition 16911 2.5.1.6 Adenyl-5'-ylimidodiphosphate competitive with ATP 29707 2.5.1.6 ADP 35-50% inhibition with 5 mM; 35-50% inhibition with 5 mM; 35-50% inhibition with 5 mM 13 2.5.1.6 Ag+ - 75 2.5.1.6 alpha,beta-methylene-adenosine tetraphosphate - 92367 2.5.1.6 alpha,beta-methylene-ATP - 7145 2.5.1.6 alpha-methyl-DL-methionine 10 mM, 18.8% inhibition 125153 2.5.1.6 AMP causes complete inactivation of the enzyme 30 2.5.1.6 ATP - 4 2.5.1.6 ATP ATP and methionine act as a switch between two different MAT III isoforms 4 2.5.1.6 ATP causes complete inactivation of the enzyme 4 2.5.1.6 Azathioprine 10 mM, 75.5% inhibition 4790 2.5.1.6 Ba2+ 70.70% residual activity at 5 mM 111 2.5.1.6 bacterial lipopolysaccharide decreases MAT activity in vivo 13394 2.5.1.6 bacterial lipopolysaccharide results in the accumulation of nitrites and nitrates in serum and in the inactivation of MAT I/III 13394 2.5.1.6 beta,gamma-methylene-ATP - 3802 2.5.1.6 Br- 93.33% residual activity at 5 mM 332 2.5.1.6 Ca2+ 86.36% residual activity at 5 mM 15 2.5.1.6 Ca2+ about 5% residual activity at 10 mM 15 2.5.1.6 carbon tetrachloride depletion of glutathione levels reduces MAT I/III activities in vivo 8476 2.5.1.6 CH3COO- 92.25% residual activity at 5 mM 15676 2.5.1.6 Cl- 85.27% residual activity at 5 mM 141 2.5.1.6 Co2+ about 45% residual activity at 10 mM 23 2.5.1.6 CTP 20 mM, 37% inhibition, S-adenosylmethionine synthetase B; 20 mM, 40% inhibition, S-adenosylmethionine synthetase A 60 2.5.1.6 CTP - 60 2.5.1.6 CTP 60-70% inhibition with 5 mM; 60-70% inhibition with 5 mM; 60-70% inhibition with 5 mM 60 2.5.1.6 Cu2+ 25.74% residual activity at 5 mM 19 2.5.1.6 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 19 2.5.1.6 Cu2+ - 19 2.5.1.6 Cu2+ complete inhibition at 10 mM 19 2.5.1.6 cycloleucine - 8077 2.5.1.6 cycloleucine 25 mM, 56% inhibition, S-adenosylmethionine synthetase A; inhibits only at sub saturating concentrations of methionine 8077 2.5.1.6 cycloleucine 10 mM, 25.8% inhibition 8077 2.5.1.6 cycloleucine competitive 8077 2.5.1.6 cycloleucine 1-aminocyclopentane-1-carboxylic acid, specific MAT inhibitor 8077 2.5.1.6 D-methionine - 957 2.5.1.6 dGTP - 219 2.5.1.6 diimidotriphosphate mechanism 57029 2.5.1.6 Dimethylsulfoxide - 985 2.5.1.6 Dimethylsulfoxide weak inhibition of liver isoenzyme 985 2.5.1.6 Dimethylsulfoxide slight inhibition of gamma isoenzyme from kidney 985 2.5.1.6 diphosphate individually a weak inhibitor, in combination with phosphate there is a marked synergistic effect 17 2.5.1.6 diphosphate - 17 2.5.1.6 diphosphate 20 mM, 30% inhibition, S-adenosylmethionine synthetase A; 20 mM, 49% inhibition, S-adenosylmethionine synthetase B 17 2.5.1.6 diphosphate inhibits high-MW isoenzyme, no effect on low-MW enzyme 17 2.5.1.6 diphosphate inhibition for S-adenosylmethionine and L-methonine 17 2.5.1.6 DL-2-Amino-trans-4-hexenoic acid - 93248 2.5.1.6 DL-Ethionine - 12516 2.5.1.6 EDTA - 21 2.5.1.6 ethanol 25 mM ethanol substantially decreases the enzymatic activity of MAT II 69 2.5.1.6 Ethionine 32-38% inhibition with 5 mM; 32-38% inhibition with 5 mM; 32-38% inhibition with 5 mM 5544 2.5.1.6 F- 88.84% residual activity at 5 mM 174 2.5.1.6 Fe2+ 59.22% residual activity at 5 mM 25 2.5.1.6 Fe2+ about 15% residual activity at 10 mM 25 2.5.1.6 Fe2+ - 25 2.5.1.6 fluorinated N,N-dialkylaminostilbene-5 i.e. FIDAS 253036 2.5.1.6 Fumarylacetoacetate reduces MAT I/III activity 15763 2.5.1.6 GDP - 53 2.5.1.6 glycerol inhibits kidney isoenzyme gamma 135 2.5.1.6 GSH causes complete inactivation of the enzyme 142 2.5.1.6 GTP 20 mM, 50% inhibition, S-adenosylmethionine synthetase B; 20 mM, 56% inhibition, S-adenosylmethionine synthetase A 37 2.5.1.6 GTP - 37 2.5.1.6 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 37 2.5.1.6 GTP competitive with respect to ATP and noncompetitive with L-methionine 37 2.5.1.6 hydrogen peroxide inactives CHO cells-MAT, prevented by desferoxamine. Time- and dose-dependent inactivation of MAT I/III, activity recovered by addition of glutathione 1126 2.5.1.6 hydrogen peroxide reduces MAT I/III activity 1126 2.5.1.6 hydrogen peroxide - 1126 2.5.1.6 I- 87.91% residual activity at 5 mM 507 2.5.1.6 K+ above 50 mM 39 2.5.1.6 K+ - 39 2.5.1.6 K+ 85.27% residual activity at 5 mM 39 2.5.1.6 L-2-Amino-4-hexynoic acid - 93766 2.5.1.6 L-2-Amino-4-methoxy-cis-but-3-enoic acid - 20322 2.5.1.6 L-2-Amino-4-methylthio-cis-but-3-enoic acid - 30105 2.5.1.6 L-buthionine-(S,R)-sulfoximine inhibits glutathione synthesis and this decreases MAT activity in vivo. Prevented by the administration of glutathione-ethyl ester 22122 2.5.1.6 L-buthionine-(S,R)-sulfoximine inactivates hepatic MAT, prevented by the administration of glutathione-ethyl ester 22122 2.5.1.6 L-ethioninamide 10 mM, 23.9% inhibition 125155 2.5.1.6 L-ethionine competitive with respect to methionine for S-adenosylmethionine formation and noncompetitive with respect to ATP 1447 2.5.1.6 L-ethionine 10 mM, 20.4% inhibition 1447 2.5.1.6 L-ethionine 1.2 mM leads to significant reduction of AdoMetS protein expression 1447 2.5.1.6 L-methionine - 88 2.5.1.6 L-methionine ATP and methionine act as a switch between two different MAT III isoforms 88 2.5.1.6 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 88 2.5.1.6 L-methionine methyl ester 10 mM, 17.7% inhibition 11008 2.5.1.6 L-methionine sulfone 10 mM, 9.2% inhibition 3081 2.5.1.6 L-methionine sulfoxide 10 mM, 4.0% inhibition 5988 2.5.1.6 L-methionine sulfoximine 10 mM, 12.6% inhibition 2748 2.5.1.6 L-Penicillamine 10 mM, 15.0% inhibition 3347 2.5.1.6 Li+ 81.40% residual activity at 5 mM 152 2.5.1.6 methanol 2.4% methanol depresses methionine adenosyltransferase specific activity, this effect is not observed with 0.8% methanol 83 2.5.1.6 methylthio propionaldehyde 10 mM, 18.4% inhibition 125154 2.5.1.6 methylthioadenosine 1 mM downregulates MAT2A expression 3648 2.5.1.6 methylthioadenosine lowers expression of MAT2A and MAT2beta 3648 2.5.1.6 Mg2+ inhibitory above 8.5 mM 6 2.5.1.6 Mn - 3649 2.5.1.6 Mn2+ inhibition in presence of Mg2+ 11 2.5.1.6 Mn2+ 73.49% residual activity at 5 mM 11 2.5.1.6 Mn2+ about 80% residual activity at 10 mM 11 2.5.1.6 additional information S-adenosyl(5')-3-methylthiopropylamine does not inhibit 2 2.5.1.6 additional information 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 2 2.5.1.6 additional information addition of reducing agents has no effect; addition of reducing agents has no effect; addition of reducing agents has no effect 2 2.5.1.6 additional information 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 2 2.5.1.6 additional information reactive oxygen and nitrogen species induce the inactivation of MAT I/III 2 2.5.1.6 additional information no inhibition with cycloleucine, L-homocysteine, L-norleucine, L-cis-2-amino-4-methoxy-3-butenoic acid, S-adenosylhomocysteine, 5'-methylthioadenosine, sinefungin 2 2.5.1.6 additional information not inhibitory: (R)-methioninol, 1,3,7-trimethyluric acid, 6-methylpurine 2 2.5.1.6 additional information no effect on activity at 0.1 mM Ni2+ 2 2.5.1.6 additional information overexpression of yeast AdoMet synthase plus cap guanine-N7 methyltransferase affords greater resistance to sinefungin than either enzyme alone 2 2.5.1.6 N-ethylmaleimide time-dependent inactivation of both MAT activities 49 2.5.1.6 Na+ in presence of Mg2+ 59 2.5.1.6 Na+ 80.16% residual activity at 5 mM 59 2.5.1.6 Ni2+ about 1% residual activity at 10 mM 38 2.5.1.6 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 662 2.5.1.6 nitric oxide inactivates hepatic MAT 662 2.5.1.6 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 62535 2.5.1.6 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 277 2.5.1.6 O-methylguanine 10 mM, 60.3% inhibition 125159 2.5.1.6 p-chloromercuribenzoate - 43 2.5.1.6 p-chloromercuribenzoate alpha and beta isoenzymes completely inhibited, gamma isoenzyme slightly inhibited 43 2.5.1.6 p-chloromercuribenzoate reduces MAT I/III activity 43 2.5.1.6 phosphate individually a weak inhibitor, in combination with diphosphate there is a synergistic inhibitory effect 16 2.5.1.6 phosphate - 16 2.5.1.6 phosphate 10 mM, 19% inhibition, S-adenosylmethionine synthetase B; 10 mM, 45% inhibition, S-adenosylmethionine synthetase A 16 2.5.1.6 phosphate competitive toward both ATP and methionine 16 2.5.1.6 putrescine 15-25% inhibition with 5 mM; 15-25% inhibition with 5 mM; 15-25% inhibition with 5 mM 155 2.5.1.6 S-adenosyl-L-ethionine - 4050 2.5.1.6 S-adenosyl-L-homocysteine - 36 2.5.1.6 S-adenosyl-L-homocysteine not inhibitory 36 2.5.1.6 S-adenosyl-L-methionine feedback inhibition of isozyme MAT II 24 2.5.1.6 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 24 2.5.1.6 S-adenosyl-L-methionine product inhibition 24 2.5.1.6 S-adenosylmethionine - 404 2.5.1.6 S-adenosylmethionine inhibition of rat kidney enzyme and rat liver MAT-II, weak inhibition of rat liver MAT-I 404 2.5.1.6 S-adenosylmethionine inhibits the A form but not the B form; non-competitive, S-adenosylmethionine synthetase A; slight inhibition of S-adenosylmethionine synthetase B 404 2.5.1.6 S-adenosylmethionine non competitive with ATP at low methionine concentration 404 2.5.1.6 S-adenosylmethionine above 0.3 mM inhibits both high-MW and low-MW isoenzymes 404 2.5.1.6 S-adenosylmethionine noncompetitive inhibitor with respect to ATP and methionine 404 2.5.1.6 S-adenosylmethionine more than 50% inhibition at 1 mM 404 2.5.1.6 S-adenosylmethionine non competitive inhibition 404 2.5.1.6 S-adenosylmethionine 5 mM downregulates MAT2A expression 404 2.5.1.6 S-adenosylmethionine lowers expression of MAT2A and MAT2beta 404 2.5.1.6 S-carbamylcysteine competitive with methionine 51140 2.5.1.6 S-nitrosoglutathione inhibits S-adenosylmethionine sinthetase activity 980 2.5.1.6 S-nitrosoglutathione inactivates MATI/III by 70% 980 2.5.1.6 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 980 2.5.1.6 S-nitrosoglutathione monoethyl ester inactivates 114412 2.5.1.6 S-nitrosylated glutathione rapid and dose-dependent loss of enzymatic activity of MAT I/III 114413 2.5.1.6 S-Trifluoromethyl-L-homocysteine - 94988 2.5.1.6 seleno-L-methionine - 9266 2.5.1.6 SIN-1 rapid and dose-dependent loss of enzymatic activity of MAT I/III 114434 2.5.1.6 Sodium diphosphate - 2669 2.5.1.6 spermidine 15-34% inhibition with 5 mM; 15-34% inhibition with 5 mM; 15-34% inhibition with 5 mM 148 2.5.1.6 spermine 30-40% inhibition with 5 mM; 30-40% inhibition with 5 mM; 30-40% inhibition with 5 mM 197 2.5.1.6 Tetrapolyphosphate 10 mM, 40% inhibition, S-adenosylmethionine synthetase B; 10 mM, 50% inhibition, S-adenosylmethionine synthetase A 3366 2.5.1.6 Tetrapolyphosphate - 3366 2.5.1.6 tripolyphosphate - 739 2.5.1.6 tripolyphosphate 1.0 mM, 57% inhibition, S-adenosylmethionine synthetase A; 1.0 mM, 62% inhibition, S-adenosylmethionine synthetase B 739 2.5.1.6 tripolyphosphate competitive with ATP and non competitive with L-methionine 739 2.5.1.6 tripolyphosphate activation or inhibition, depending on isoenzyme, S-adenosylmethionine and tripolyphosphate concentration 739 2.5.1.6 tripolyphosphate competitive with ATP 739 2.5.1.6 tripolyphosphate strong inhibitor; strong inhibitor; strong inhibitor 739 2.5.1.6 tripolyphosphate competitive with ATP; non competitive with L-methionine 739 2.5.1.6 TTP - 523 2.5.1.6 uric acid 10 mM, 45.6% inhibition 1421 2.5.1.6 UTP - 65 2.5.1.6 xanthine 10 mM, 35.4% inhibition 234 2.5.1.6 Zn2+ 22.17% residual activity at 5 mM 14 2.5.1.6 Zn2+ about 10% residual activity at 10 mM 14