2.0 2012-07-30 14:54:59 -0600 2015-09-17 15:41:17 -0600 ECMDB21221 M2MDB001629 Glutathione disulfide Glutathione (GSH) is a tripeptide with a gamma peptide linkage between the amine group of cysteine (which is attached by normal peptide linkage to a glycine) and the carboxyl group of the glutamate side-chain. It is an antioxidant, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides. Glutathione is a cofactor for the enzyme glutathione peroxidase. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase (EC 3.1.2.6) catalyzes the hydrolysis of S-D-Lactoyl-glutathione to glutathione and D-lactate.; Glutathione disulfide (GSSG) is a disulfide derived from two glutathione molecules. (2S,2'S)-5,5'-[disulfanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoate) (2S,2'S)-5,5'-[disulfanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoate) (non-preferred name) (2S,2'S)-5,5'-[disulfanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoic acid) (2S,2'S)-5,5'-[disulfanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoic acid) (non-preferred name) (2S,2'S)-5,5'-[disulphanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoate) (2S,2'S)-5,5'-[disulphanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoate) (non-preferred name) (2S,2'S)-5,5'-[disulphanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoic acid) (2S,2'S)-5,5'-[disulphanediylbis({(2R)-3-[(carboxymethyl)amino]-3-oxopropane-1,2-diyl}imino)]bis(2-amino-5-oxopentanoic acid) (non-preferred name) Glutathione disulfide Glutathione disulphide Glutathione ox Glutathione oxidized GSSG L(-)-Glutathione(oxidized) L-Glutathione oxidized Oxidised glutathione Oxidized glutathione OXIDIZED GLUTATHIONE DISULFIDE OXIDIZED glutathione disulphide Oxiglutatione C20H32N6O12S2 612.631 612.151961898 2-amino-4-[(2-{[2-(4-amino-4-carboxybutanamido)-2-[(carboxymethyl)carbamoyl]ethyl]disulfanyl}-1-[(carboxymethyl)carbamoyl]ethyl)carbamoyl]butanoic acid oxiglutatione 27025-41-8 NC(CCC(=O)NC(CSSCC(NC(=O)CCC(N)C(O)=O)C(=O)NCC(O)=O)C(=O)NCC(O)=O)C(O)=O InChI=1S/C20H32N6O12S2/c21-9(19(35)36)1-3-13(27)25-11(17(33)23-5-15(29)30)7-39-40-8-12(18(34)24-6-16(31)32)26-14(28)4-2-10(22)20(37)38/h9-12H,1-8,21-22H2,(H,23,33)(H,24,34)(H,25,27)(H,26,28)(H,29,30)(H,31,32)(H,35,36)(H,37,38) YPZRWBKMTBYPTK-UHFFFAOYSA-N Solid Cytosol Extra-organism Periplasm logp -3.60 ALOGPS logs -3.18 ALOGPS solubility 4.06e-01 g/l ALOGPS logp -10 ChemAxon pka_strongest_acidic 1.44 ChemAxon pka_strongest_basic 9.61 ChemAxon iupac 2-amino-4-[(2-{[2-(4-amino-4-carboxybutanamido)-2-[(carboxymethyl)carbamoyl]ethyl]disulfanyl}-1-[(carboxymethyl)carbamoyl]ethyl)carbamoyl]butanoic acid ChemAxon average_mass 612.631 ChemAxon mono_mass 612.151961898 ChemAxon smiles NC(CCC(=O)NC(CSSCC(NC(=O)CCC(N)C(O)=O)C(=O)NCC(O)=O)C(=O)NCC(O)=O)C(O)=O ChemAxon formula C20H32N6O12S2 ChemAxon inchi InChI=1S/C20H32N6O12S2/c21-9(19(35)36)1-3-13(27)25-11(17(33)23-5-15(29)30)7-39-40-8-12(18(34)24-6-16(31)32)26-14(28)4-2-10(22)20(37)38/h9-12H,1-8,21-22H2,(H,23,33)(H,24,34)(H,25,27)(H,26,28)(H,29,30)(H,31,32)(H,35,36)(H,37,38) ChemAxon inchikey YPZRWBKMTBYPTK-UHFFFAOYSA-N ChemAxon polar_surface_area 317.64 ChemAxon refractivity 136.65 ChemAxon polarizability 58.43 ChemAxon rotatable_bond_count 21 ChemAxon acceptor_count 14 ChemAxon donor_count 10 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Glutathione metabolism The biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione. This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione. PW000833 ec00480 Metabolic Arachidonic acid metabolism Delete Pathway Arachidonate (arachidonic acid) is a polyunsaturated ω-6 fatty acid with a 20-carbon chain and four cis-double bonds. It is produced at high levels by mosses, some plants, and by some marine bacteria. Mammals cannot synthesize arachidonate de novo, but most mammals are able to synthesize it from simpler unsaturated fatty acids. In addition to being involved in cellular signaling as a lipid second messenger, arachidonate is also a key inflammatory intermediate and can also act as a vasodilator. Like other fatty acids, arachidonate is rarely found in its free form. It is usually found either as arachidonoyl-CoA or incorporated into a lipid. It is produced from phosphatidylcholine through a phospholipase A1 PW000759 ec00590 Metabolic Selenium metabolism The selenium metabolism begins with the introduction of selenate and selenite to the cytosol through a sulphate permease system. Once in the cell, selenate can be reduced to selenite through nitrate reductases A and Z. Selenite then interacts with glutathione and 2 hydrogen ions resulting in the release of 2 water molecules, a hydroxide molecule, a glutathione disulfide and a selenodiglutathione. The latter compound then reacts with NADPH+H resulting in the release of a NADP, a glutathione and a glutathioselenol. Glutathiolselenol can then be oxidize resulting in a a glutathiolselenol ion which can then interact with a water molecule resulting in a release of glutathion and selenium Glutathiolselenol can also react with NADPH and hydrogen ion resulting in a release of glutathione, NADP, a hydroxide molecule and a hydrogen selenide. This compound can react in a reversible reaction by being oxidized resulting in a hydrogen selenide ion . This compound can then be phosphorylated by interacting with an ATP and releasing a AMP, a phosphate and a selenophosphate. PW001894 Metabolic glutathione metabolism II The biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione. This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione. Glutathione can then be degraded into various different glutathione containg compounds by reacting with a napthalene through a glutathione S-transferase PW001927 Metabolic glutathione metabolism III The biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione. This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione. PW002018 Metabolic glutathione redox reactions II GLUT-REDOX-PWY Specdb::CMs 26116 Specdb::CMs 38575 Specdb::CMs 102671 Specdb::CMs 102672 Specdb::NmrOneD 5186 Specdb::NmrOneD 269318 Specdb::NmrOneD 269319 Specdb::NmrOneD 269320 Specdb::NmrOneD 269321 Specdb::NmrOneD 269322 Specdb::NmrOneD 269323 Specdb::NmrOneD 269324 Specdb::NmrOneD 269325 Specdb::NmrOneD 269326 Specdb::NmrOneD 269327 Specdb::NmrOneD 269328 Specdb::NmrOneD 269329 Specdb::NmrOneD 269330 Specdb::NmrOneD 269331 Specdb::NmrOneD 269332 Specdb::NmrOneD 269333 Specdb::NmrOneD 269334 Specdb::NmrOneD 269335 Specdb::NmrOneD 269336 Specdb::NmrOneD 269337 Specdb::MsMs 178233 Specdb::MsMs 178234 Specdb::MsMs 178235 Specdb::MsMs 180549 Specdb::MsMs 180550 Specdb::MsMs 180551 Specdb::MsMs 1218180 Specdb::MsMs 1218181 Specdb::MsMs 1218182 Specdb::MsMs 1218183 Specdb::MsMs 1218184 Specdb::MsMs 1218185 Specdb::MsMs 1218186 Specdb::MsMs 1218187 Specdb::MsMs 1218188 Specdb::MsMs 1218189 Specdb::MsMs 1218190 Specdb::MsMs 1218191 Specdb::MsMs 1218192 HMDB03337 975 58835 C00127 17858 OXIDIZED-GLUTATHIONE GDS Glutathione_disulfide Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. 17379776 http://hmdb.ca/system/metabolites/msds/000/002/918/original/HMDB03337.pdf?1358462601 Vitamin B12 transport periplasmic protein BtuE P06610 BTUE_ECOLI btuE http://ecmdb.ca/proteins/P06610.xml Glutathione reductase P06715 GSHR_ECOLI gor http://ecmdb.ca/proteins/P06715.xml Arsenate reductase P0AB96 ARSC_ECOLI arsC http://ecmdb.ca/proteins/P0AB96.xml Thiol:disulfide interchange protein DsbG P77202 DSBG_ECOLI dsbG http://ecmdb.ca/proteins/P77202.xml Glutaredoxin-4 P0AC69 GLRX4_ECOLI grxD http://ecmdb.ca/proteins/P0AC69.xml Thiol:disulfide interchange protein DsbC P0AEG6 DSBC_ECOLI dsbC http://ecmdb.ca/proteins/P0AEG6.xml Glutaredoxin-3 P0AC62 GLRX3_ECOLI grxC http://ecmdb.ca/proteins/P0AC62.xml Glutaredoxin-2 P0AC59 GLRX2_ECOLI grxB http://ecmdb.ca/proteins/P0AC59.xml Glutaredoxin-1 P68688 GLRX1_ECOLI grxA http://ecmdb.ca/proteins/P68688.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml glutaredoxin + 2 Glutathione > glutaredoxin + Glutathione disulfide Arsenate + 2 Glutathione > Arsenite + Glutathione disulfide + Water periplasmic disulfide isomerase/thiol-disulphide oxidase (oxidized) + 2 Glutathione > periplasmic disulfide isomerase/thiol-disulphide oxidase (reduced) + Glutathione disulfide 2 Glutathione + Hydrogen peroxide <> Glutathione disulfide +2 Water R00274 GLUTATHIONE-PEROXIDASE-RXN protein disulfide isomerase II (oxidized) + 2 Glutathione > protein disulfide isomerase II (reduced) + Glutathione disulfide Glutathione disulfide + Hydrogen ion + NADPH <>2 Glutathione + NADP R00115 GLUTATHIONE-REDUCT-NADPH-RXN 2 Glutathione + NAD <> Glutathione disulfide + NADH + Hydrogen ion R00094 2 Glutathione + NADP <> Glutathione disulfide + NADPH + Hydrogen ion R00115 2 Glutathione + 5(S)-Hydroperoxyeicosatetraenoic acid <> Glutathione disulfide + 5-HETE + Water R07034 2 Glutathione + 15(S)-HPETE <> Glutathione disulfide + 15(S)-HETE + Water R07035 Selenite + Glutathione + Hydrogen ion > Selenodiglutathione + Glutathione disulfide + Water RXN-12864 2-hydroxyethyldisulfide + Glutathione 2-mercaptoethanol + Glutathione disulfide RXN0-6256 Hydrogen peroxide + Glutathione > Glutathione disulfide + Water GLUTATHIONE-PEROXIDASE-RXN Glutathione + NADP < Glutathione disulfide + NADPH + Hydrogen ion GLUTATHIONE-REDUCT-NADPH-RXN 2 Glutathione + NADP > Glutathione disulfide + NADPH Oxidized glutathione + Hydrogen ion + NADPH + Glutathione disulfide + NADPH > NADP +2 Glutathione PW_R003055 Glutathione disulfide + Hydrogen ion + NADPH <>2 Glutathione + NADP Glutathione disulfide + Hydrogen ion + NADPH <>2 Glutathione + NADP Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucose Shake flask and filter culture 2370.0 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 9480000 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerol Shake flask and filter culture 7310.0 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 29240000 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetate Shake flask and filter culture 1680.0 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 6720000 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 48 mM Na2HPO4, 22 mM KH2PO4, 10 mM NaCl, 45 mM (NH4)2SO4, supplemented with 1 mM MgSO4, 1 mg/l thiamine·HCl, 5.6 mg/l CaCl2, 8 mg/l FeCl3, 1 mg/l MnCl2·4H2O, 1.7 mg/l ZnCl2, 0.43 mg/l CuCl2·2H2O, 0.6 mg/l CoCl2·2H2O and 0.6 mg/l Na2MoO4·2H2O. 4 g/L Gluco Bioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h 3670.0 uM 0.0 37 oC BW25113 Stationary Phase, glucose limited 14680000 0 Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597. 17379776