2.02012-07-30 14:54:59 -06002015-09-17 15:41:17 -0600ECMDB21221M2MDB001629Glutathione disulfideGlutathione (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 disulfideGlutathione disulphideGlutathione oxGlutathione oxidizedGSSGL(-)-Glutathione(oxidized)L-Glutathione oxidizedOxidised glutathioneOxidized glutathioneOXIDIZED GLUTATHIONE DISULFIDEOXIDIZED glutathione disulphideOxiglutationeC20H32N6O12S2612.631612.1519618982-amino-4-[(2-{[2-(4-amino-4-carboxybutanamido)-2-[(carboxymethyl)carbamoyl]ethyl]disulfanyl}-1-[(carboxymethyl)carbamoyl]ethyl)carbamoyl]butanoic acidoxiglutatione27025-41-8NC(CCC(=O)NC(CSSCC(NC(=O)CCC(N)C(O)=O)C(=O)NCC(O)=O)C(=O)NCC(O)=O)C(O)=OInChI=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-NSolidCytosolExtra-organismPeriplasmlogp-3.60logs-3.18solubility4.06e-01 g/llogp-10pka_strongest_acidic1.44pka_strongest_basic9.61iupac2-amino-4-[(2-{[2-(4-amino-4-carboxybutanamido)-2-[(carboxymethyl)carbamoyl]ethyl]disulfanyl}-1-[(carboxymethyl)carbamoyl]ethyl)carbamoyl]butanoic acidaverage_mass612.631mono_mass612.151961898smilesNC(CCC(=O)NC(CSSCC(NC(=O)CCC(N)C(O)=O)C(=O)NCC(O)=O)C(=O)NCC(O)=O)C(O)=OformulaC20H32N6O12S2inchiInChI=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)inchikeyYPZRWBKMTBYPTK-UHFFFAOYSA-Npolar_surface_area317.64refractivity136.65polarizability58.43rotatable_bond_count21acceptor_count14donor_count10physiological_charge-2formal_charge0Glutathione metabolismThe 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.
PW000833ec00480MetabolicArachidonic acid metabolismDelete 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 A1PW000759ec00590MetabolicSelenium metabolismThe 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.PW001894Metabolicglutathione metabolism IIThe 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
PW001927Metabolicglutathione metabolism IIIThe 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.
PW002018Metabolicglutathione redox reactions IIGLUT-REDOX-PWYSpecdb::CMs26116Specdb::CMs38575Specdb::CMs102671Specdb::CMs102672Specdb::NmrOneD5186Specdb::NmrOneD269318Specdb::NmrOneD269319Specdb::NmrOneD269320Specdb::NmrOneD269321Specdb::NmrOneD269322Specdb::NmrOneD269323Specdb::NmrOneD269324Specdb::NmrOneD269325Specdb::NmrOneD269326Specdb::NmrOneD269327Specdb::NmrOneD269328Specdb::NmrOneD269329Specdb::NmrOneD269330Specdb::NmrOneD269331Specdb::NmrOneD269332Specdb::NmrOneD269333Specdb::NmrOneD269334Specdb::NmrOneD269335Specdb::NmrOneD269336Specdb::NmrOneD269337Specdb::MsMs178233Specdb::MsMs178234Specdb::MsMs178235Specdb::MsMs180549Specdb::MsMs180550Specdb::MsMs180551Specdb::MsMs1218180Specdb::MsMs1218181Specdb::MsMs1218182Specdb::MsMs1218183Specdb::MsMs1218184Specdb::MsMs1218185Specdb::MsMs1218186Specdb::MsMs1218187Specdb::MsMs1218188Specdb::MsMs1218189Specdb::MsMs1218190Specdb::MsMs1218191Specdb::MsMs1218192HMDB0333797558835C0012717858OXIDIZED-GLUTATHIONEGDSGlutathione_disulfideKeseler, 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-D590.21097882van 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 370:17-25.17765195Bennett, 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 5:593-599.19561621Ishii, 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 316:593-597.17379776http://hmdb.ca/system/metabolites/msds/000/002/918/original/HMDB03337.pdf?1358462601Vitamin B12 transport periplasmic protein BtuEP06610BTUE_ECOLIbtuEhttp://ecmdb.ca/proteins/P06610.xmlGlutathione reductaseP06715GSHR_ECOLIgorhttp://ecmdb.ca/proteins/P06715.xmlArsenate reductaseP0AB96ARSC_ECOLIarsChttp://ecmdb.ca/proteins/P0AB96.xmlThiol:disulfide interchange protein DsbGP77202DSBG_ECOLIdsbGhttp://ecmdb.ca/proteins/P77202.xmlGlutaredoxin-4P0AC69GLRX4_ECOLIgrxDhttp://ecmdb.ca/proteins/P0AC69.xmlThiol:disulfide interchange protein DsbCP0AEG6DSBC_ECOLIdsbChttp://ecmdb.ca/proteins/P0AEG6.xmlGlutaredoxin-3P0AC62GLRX3_ECOLIgrxChttp://ecmdb.ca/proteins/P0AC62.xmlGlutaredoxin-2P0AC59GLRX2_ECOLIgrxBhttp://ecmdb.ca/proteins/P0AC59.xmlGlutaredoxin-1P68688GLRX1_ECOLIgrxAhttp://ecmdb.ca/proteins/P68688.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlglutaredoxin + 2 Glutathione > glutaredoxin + Glutathione disulfideArsenate + 2 Glutathione > Arsenite + Glutathione disulfide + Waterperiplasmic disulfide isomerase/thiol-disulphide oxidase (oxidized) + 2 Glutathione > periplasmic disulfide isomerase/thiol-disulphide oxidase (reduced) + Glutathione disulfide2 Glutathione + Hydrogen peroxide <> Glutathione disulfide +2 WaterR00274GLUTATHIONE-PEROXIDASE-RXNprotein disulfide isomerase II (oxidized) + 2 Glutathione > protein disulfide isomerase II (reduced) + Glutathione disulfideGlutathione disulfide + Hydrogen ion + NADPH <>2 Glutathione + NADPR00115GLUTATHIONE-REDUCT-NADPH-RXN2 Glutathione + NAD <> Glutathione disulfide + NADH + Hydrogen ionR000942 Glutathione + NADP <> Glutathione disulfide + NADPH + Hydrogen ionR001152 Glutathione + 5(S)-Hydroperoxyeicosatetraenoic acid <> Glutathione disulfide + 5-HETE + WaterR070342 Glutathione + 15(S)-HPETE <> Glutathione disulfide + 15(S)-HETE + WaterR07035Selenite + Glutathione + Hydrogen ion > Selenodiglutathione + Glutathione disulfide + WaterRXN-128642-hydroxyethyldisulfide + Glutathione 2-mercaptoethanol + Glutathione disulfideRXN0-6256Hydrogen peroxide + Glutathione > Glutathione disulfide + WaterGLUTATHIONE-PEROXIDASE-RXNGlutathione + NADP < Glutathione disulfide + NADPH + Hydrogen ionGLUTATHIONE-REDUCT-NADPH-RXN2 Glutathione + NADP > Glutathione disulfide + NADPHOxidized glutathione + Hydrogen ion + NADPH + Glutathione disulfide + NADPH > NADP +2 GlutathionePW_R003055Glutathione disulfide + Hydrogen ion + NADPH <>2 Glutathione + NADPGlutathione disulfide + Hydrogen ion + NADPH <>2 Glutathione + NADPGutnick 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 glucoseShake flask and filter culture2370.0uM0.037 oCK12 NCM3722Mid-Log Phase94800000Bennett, 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 5:593-599.19561621Gutnick 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 glycerolShake flask and filter culture7310.0uM0.037 oCK12 NCM3722Mid-Log Phase292400000Bennett, 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 5:593-599.19561621Gutnick 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 acetateShake flask and filter culture1680.0uM0.037 oCK12 NCM3722Mid-Log Phase67200000Bennett, 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 5:593-599.1956162148 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 GlucoBioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h3670.0uM0.037 oCBW25113Stationary Phase, glucose limited146800000Ishii, 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