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MetaCyc Compound: glutathione

Synonyms: γ-L-glutamyl-L-cysteinyl-glycine, GSH, reduced glutathione, glutathionate

Superclasses: an organosulfur compound all glutathiones

Chemical Formula: C10H16N3O6S

Molecular Weight: 306.31 Daltons

Monoisotopic Molecular Weight: 307.0838059839 Daltons

SMILES: C(S)C(C(NCC([O-])=O)=O)NC(=O)CCC([N+])C([O-])=O

InChI: InChI=1S/C10H17N3O6S/c11-5(10(18)19)1-2-7(14)13-6(4-20)9(17)12-3-8(15)16/h5-6,20H,1-4,11H2,(H,12,17)(H,13,14)(H,15,16)(H,18,19)/p-1/t5-,6-/m0/s1

InChIKey: InChIKey=RWSXRVCMGQZWBV-WDSKDSINSA-M

Unification Links: CAS:70-18-8 , ChEBI:57925 , ChemSpider:19589806 , HMDB:HMDB00125 , IAF1260:33669 , KEGG:C00051 , KNApSAcK:C00001518 , MetaboLights:MTBLC57925 , PubChem:20756463

Standard Gibbs Free Energy of Change Formation (ΔfG in kcal/mol): -56.924126 Inferred by computational analysis [Latendresse13]

Reactions known to consume the compound:

4-hydroxy-2-nonenal detoxification :
glutathione + 4-hydroxy-2-nonenal → 4-hydroxy-2-nonenal-glutathione conjugate

arsenate detoxification I (glutaredoxin) :
2 glutathione + methylarsonate → glutathione disulfide + methylarsonite

ascorbate glutathione cycle , ascorbate recycling (cytosolic) :
L-dehydro-ascorbate + 2 glutathione → L-ascorbate + glutathione disulfide + H+

camalexin biosynthesis :
indole-3-acetonitrile + glutathione → indole-3-acetonitrile-glutatione conjugate + 2 H+

drosopterin and aurodrosopterin biosynthesis :
2-amino-6-acetyl-3,7,8,9-tetrahydro-3H-pyrimido[4,5-b][1,4]diazepin-4-one + glutathione disulfide + H2O ← 6-pyruvoyl tetrahydropterin + 2 glutathione

γ-glutamyl cycle :
glutathione + a standard α amino acid → L-cysteinyl-glycine + an (γ-L-glutamyl)-L-amino acid

gliotoxin biosynthesis :
3-benzyl-3,6-dihydroxy-6-(hydroxymethyl)-diketopiperazine + 2 glutathione → 3-benzyl-3,6 -bis(glutathione)- 6-(hydroxymethyl)-diketopiperazine + 2 H2O

glucosinolate biosynthesis from dihomomethionine :
5-methylthiopentanonitrile oxide + glutathione → 5-methylthiopentylhydroximoyl-glutathione

glucosinolate biosynthesis from hexahomomethionine :
9-methylthiononanonitrile oxide + glutathione → 9-methylthiononylhydroximoyl-glutathione

glucosinolate biosynthesis from homomethionine :
4-methylthiobutanonitrile oxide + glutathione → 4-methylthiobutylhydroximoyl-glutathione

glucosinolate biosynthesis from pentahomomethionine :
8-methylthiooctanonitrile oxide + glutathione → 8-methylthiooctylhydroximoyl-glutathione

glucosinolate biosynthesis from phenylalanine :
phenylacetonitrile oxide + glutathione → phenylacetohydroximoyl-glutathione

glucosinolate biosynthesis from tetrahomomethionine :
7-methylthioheptanonitrile oxide + glutathione → 7-methylthioheptylhydroximoyl-glutathione

glucosinolate biosynthesis from trihomomethionine :
6-methylthiohexanonitrile oxide + glutathione → 6-methylthiohexylhydroximoyl-glutathione

glucosinolate biosynthesis from tryptophan :
indole-3-acetonitrile oxide + glutathione → indole-3-acetohydroximoyl-glutathione

glutathione degradation (DUG pathway - yeast) :
glutathione + H2O → L-cysteinyl-glycine + L-glutamate

glutathione redox reactions I :
a lipid hydroperoxide + 2 glutathione + H+ → a lipid + glutathione disulfide + 2 H2O
hydrogen peroxide + 2 glutathione → glutathione disulfide + 2 H2O

glutathione redox reactions II :
2 glutathione + an oxidized glutaredoxin → glutathione disulfide + a reduced glutaredoxin

glutathione-mediated detoxification I , glutathione-mediated detoxification II :
glutathione + RX → a glutathione-toxin conjugate + HX

glutathionylspermidine biosynthesis :
spermidine + glutathione + ATP → glutathionylspermidine + ADP + phosphate + H+

guaiacylglycerol-β-guaiacyl ether degradation :
α-glutathionyl-β-hydroxypropiovanillone II + glutathione → β-hydroxypropiovanillone + glutathione disulfide
α-glutathionyl-β-hydroxypropiovanillone I + glutathione → β-hydroxypropiovanillone + glutathione disulfide
(-)-(βR)-MPHPV + glutathione → α-glutathionyl-β-hydroxypropiovanillone II + guaiacol
(+)-(βS)-MPHPV + glutathione → α-glutathionyl-β-hydroxypropiovanillone I + guaiacol

homophytochelatin biosynthesis :
glutathione + homoglutathione → γ-Glu-Cys-γ-Glu-Cys-β-Ala + glycine

hypoglycin biosynthesis :
glutathione + hypoglycin A → L-cysteinyl-glycine + hypoglycin B

indole glucosinolate breakdown (active in intact plant cell) :
4-methoxy-3-indolylmethylisothiocyanate + glutathione → 4-methoxy-3-indolylmethylisothiocyanate-glutathione
indolylmethylisothiocyanate + glutathione → indol-3-ylmethylisothiocyanate-glutathione

indole glucosinolate breakdown (insect chewing induced) :
indole-3-carbinol + glutathione → indol-3-ylmethyl-glutathione + H2O

leukotriene biosynthesis :
leukotriene-C4 ← leukotriene A4 + glutathione

pentachlorophenol degradation :
2,3,6-trichlorohydroquinone + 2 glutathione → 2,6-dichloro-p-hydroquinone + chloride + glutathione disulfide + H+

phytochelatins biosynthesis :
[Glu(-Cys)]n-Gly + glutathione → [Glu(-Cys)](n+1)-Gly + glycine

reactive oxygen species degradation (mammalian) :
hydrogen peroxide + 2 glutathione → glutathione disulfide + 2 H2O

selenate reduction :
selenite + AMP + glutathione disulfide + 3 H+ ← adenosine 5'-phosphoselenate + 2 glutathione
selenite + 4 glutathione + 2 H+ → selenodiglutathione + glutathione disulfide + 3 H2O

sulfate reduction II (assimilatory) :
sulfite + AMP + glutathione disulfide + 2 H+ ← adenosine 5'-phosphosulfate + 2 glutathione

sulfur oxidation I (aerobic) , sulfur oxidation II (Fe+3-dependent) :
glutathione + S0 → S-sulfanylglutathione

superpathway of sulfide oxidation (Acidithiobacillus ferrooxidans) :
glutathione + intracellular S0 → S-sulfanylglutathione

trypanothione biosynthesis :
glutathione + glutathionylspermidine + ATP → trypanothione + ADP + phosphate + H+

Not in pathways:
glutathione[periplasmic space] + H2O[periplasmic space] → L-cysteinyl-glycine[periplasmic space] + L-glutamate[periplasmic space]
2 glutathione + oxygen → glutathione disulfide + hydrogen peroxide

Reactions known to produce the compound:

formaldehyde oxidation II (glutathione-dependent) :
S-formylglutathione + H2O → formate + glutathione + H+

glutathione biosynthesis :
glycine + γ-L-glutamyl-L-cysteine + ATP → glutathione + ADP + phosphate + H+

glutathione redox reactions I , glutathione redox reactions II :
2 glutathione + NADP+ ← glutathione disulfide + NADPH + H+

methylglyoxal degradation I :
(R)-S-lactoylglutathione + H2O ↔ glutathione + (R)-lactate + H+

selenate reduction :
selenodiglutathione + NADPH + H+ → glutathioselenol + glutathione + NADP+
hydrogen selenide + glutathione + NADP+ ← glutathioselenol + NADPH + H+

sulfide oxidation III (sulfur dioxygenase) :
S-sulfanylglutathione + oxygen + H2O → glutathione + sulfite + 2 H+
hydrogen sulfide + glutathione disulfide → S-sulfanylglutathione + glutathione

sulfur oxidation I (aerobic) :
S-sulfanylglutathione + oxygen + H2O → glutathione + sulfite + 2 H+

sulfur oxidation II (Fe+3-dependent) :
S-sulfanylglutathione + 4 Fe3+ + 3 H2O → sulfite + glutathione + 4 Fe2+ + 6 H+

Not in pathways:
S-succinylglutathione + H2O → succinate + glutathione + H+
an S-acylglutathione + H2O → a carboxylate + glutathione
S-(2-hydroxyacyl)glutathione + H2O → glutathione + a 2-hydroxy carboxylate

Reactions known to both consume and produce the compound:

formaldehyde oxidation II (glutathione-dependent) :
S-hydroxymethylglutathione → formaldehyde + glutathione

γ-hexachlorocyclohexane degradation :
2,5-dichloro-p-quinol + 2 glutathione ↔ chlorohydroquinone + glutathione disulfide + chloride + H+

methylglyoxal degradation I :
(R)-S-lactoylglutathione ↔ methylglyoxal + glutathione

pentachlorophenol degradation :
tetrachlorohydroquinone + 2 glutathione ↔ 2,3,6-trichlorohydroquinone + chloride + glutathione disulfide

Not in pathways:
glutathionylspermidine + H2O ↔ glutathione + spermidine
1-chloro-2,4-dinitrobenzene + glutathione ↔ 2,4-dinitrophenyl-S-glutathione + chloride + H+

In Reactions of unknown directionality:

homophytochelatin biosynthesis :
[Glu(-Cys)]n-β-Ala + glutathione = [Glu(-Cys)](n+1)-β-Ala + glycine

Not in pathways:
glutathione disulfide + coenzyme A = glutathione + CoA-glutathione
S-glutathionyl-L-cysteine + NADPH + H+ = L-cysteine + glutathione + NADP+
a xanthine dehydrogenase + glutathione disulfide = a xanthine oxidase + 2 glutathione
chloride + glutathione disulfide + benzene-1,4-diol + H+ = chlorohydroquinone + 2 glutathione
D-cystine + 2 glutathione = glutathione disulfide + 2 D-cysteine
GS-methylhydroquinone + glutathione = methyl-p-hydroquinone + glutathione disulfide
thiosulfate + 2 glutathione = sulfite + hydrogen sulfide + glutathione disulfide + H+
2-hydroxyethyldisulfide + 2 glutathione = 2 2-mercaptoethanol + glutathione disulfide
bromoacetate + glutathione = glutathione-S-acetate + bromide + H+
2 glutathione + a protein disulfide = glutathione disulfide + a protein dithiol
glutathione + coenzyme A + NADP+ = CoA-glutathione + NADPH + H+
adenosine 5'-phosphosulfate + glutathione = AMP + glutathione-sulfite + H+
S-sulfo-L-cysteine + glutathione + H2O = S-glutathionyl-L-cysteine + sulfate + 3 H+
homocystine + 2 glutathione = glutathione disulfide + 2 L-homocysteine
L-cystine + 2 glutathione = glutathione disulfide + 2 L-cysteine

In Transport reactions:
glutathione[cytosol] + ATP + H2O → glutathione[periplasmic space] + ADP + phosphate + H+ ,
glutathione[periplasmic space] + ATP + H2O → glutathione[cytosol] + ADP + phosphate + H+

Enzymes activated by glutathione, sorted by the type of activation, are:

Activator (Allosteric) of: dimethylsulfoniopropionate lyase [Cantoni56] , cis-benzene glycol dehydrogenase [Axcell73]

Activator (Mechanism unknown) of: L-xylulose kinase [Sanchez94] , acetylornithine deacetylase [Boyen92] , methylglyoxal reductase (NADPH-dependent) [Saikusa87] , scyllo-inosose dehydratase [Yoshida04] , sequoyitol dehydrogenase [Ruis69] , deacetoxycephalosporin C hydroxylase [Baker91] , isopenicillin N synthase [Perry88] , L-asparaginase [Raha90]

Enzymes inhibited by glutathione, sorted by the type of inhibition, are:

Inhibitor (Competitive) of: S-formylglutathione hydrolase [Uotila74] , dopamine β-monooxygenase [Comment 1]

Inhibitor (Noncompetitive) of: glutamate-cysteine ligase [Jez04] , glutathione synthetase [Jez04a]

Inhibitor (Mechanism unknown) of: aspartate semialdehyde dehydrogenase [Alvarez04] , 2-amino-3-ketobutyrate CoA ligase [Mukherjee87] , glutamate-cysteine ligase [Apontoweil75] , [thyroglobulin]-3,5-diiodotyrosine synthase [Coval67] , ethylnitronate monooxygenase [Gorlatova98] , glutamate--cysteine ligase , glutamate--cysteine ligase [Misra98] , γ-glutamyl transpeptidase [Miller76] , tellimagrandin II: O2 oxidoreductase [Niemetz03] , pentagalloylglucose: O2 oxidoreductase [Niemetz03a] , ethylnitronate monooxygenase [Kido84] , benzalacetone synthase [BorejszaWysocki96]

This compound has been characterized as a cofactor or prosthetic group of the following enzymes: cytoplasmic arsenate reductase , maleylpyruvate isomerase , 2-hydroxychromene-2-carboxylate isomerase , p-hydroxyphenylpyruvate oxidase , maleylacetoacetate isomerase , maleylacetoacetate isomerase , maleylacetoacetate isomerase , methylarsonate reductase , dimethylarsinate reductase

Credits:
Revised 12-Mar-2012 by Caspi R , SRI International


References

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Apontoweil75: Apontoweil P, Berends W (1975). "Glutathione biosynthesis in Escherichia coli K 12. Properties of the enzymes and regulation." Biochim Biophys Acta 1975;399(1);1-9. PMID: 238647

Axcell73: Axcell BC, Geary PJ (1973). "The metabolism of benzene by bacteria. Purification and some properties of the enzyme cis-1,2-dihydroxycyclohexa-3,5-diene (nicotinamide adenine dinucleotide) oxidoreductase (cis-benzene glycol dehydrogenase)." Biochem J 136(4);927-34. PMID: 4362337

Baker91: Baker BJ, Dotzlaf JE, Yeh WK (1991). "Deacetoxycephalosporin C hydroxylase of Streptomyces clavuligerus. Purification, characterization, bifunctionality, and evolutionary implication." J Biol Chem 266(8);5087-93. PMID: 2002049

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Boyen92: Boyen A, Charlier D, Charlier J, Sakanyan V, Mett I, Glansdorff N (1992). "Acetylornithine deacetylase, succinyldiaminopimelate desuccinylase and carboxypeptidase G2 are evolutionarily related." Gene 1992;116(1);1-6. PMID: 1628835

Cantoni56: Cantoni GL, Anderson, DG (1956). "Enzymatic cleavage of dimethylpropiothetin by Polysiphonia lanosa." J Biol Chem 222(1);171-7. PMID: 13366990

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Gorlatova98: Gorlatova N, Tchorzewski M, Kurihara T, Soda K, Esaki N (1998). "Purification, characterization, and mechanism of a flavin mononucleotide-dependent 2-nitropropane dioxygenase from Neurospora crassa." Appl Environ Microbiol 1998;64(3);1029-33. PMID: 9501443

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Jez04a: Jez JM, Cahoon RE (2004). "Kinetic mechanism of glutathione synthetase from Arabidopsis thaliana." J Biol Chem 279(41);42726-31. PMID: 15302873

Kido84: Kido T, Soda K (1984). "Oxidation of anionic nitroalkanes by flavoenzymes, and participation of superoxide anion in the catalysis." Arch Biochem Biophys 234(2);468-75. PMID: 6149727

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Miller76: Miller SP, Awasthi YC, Srivastava SK (1976). "Studies of human kidney gamma-glutamyl transpeptidase. Purification and structural, kinetic and immunological properties." J Biol Chem 251(8);2271-8. PMID: 4442

Misra98: Misra I, Griffith OW (1998). "Expression and purification of human gamma-glutamylcysteine synthetase." Protein Expr Purif 13(2);268-76. PMID: 9675072

Mukherjee87: Mukherjee JJ, Dekker EE (1987). "Purification, properties, and N-terminal amino acid sequence of homogeneous Escherichia coli 2-amino-3-ketobutyrate CoA ligase, a pyridoxal phosphate-dependent enzyme." J Biol Chem 1987;262(30);14441-7. PMID: 3117785

Niemetz03: Niemetz R, Gross GG (2003). "Ellagitannin biosynthesis: laccase-catalyzed dimerization of tellimagrandin II to cornusiin E in Tellima grandiflora." Phytochemistry 64(7);1197-201. PMID: 14599517

Niemetz03a: Niemetz R, Gross GG (2003). "Oxidation of pentagalloylglucose to the ellagitannin, tellimagrandin II, by a phenol oxidase from Tellima grandiflora leaves." Phytochemistry 62(3);301-6. PMID: 12620341

Perry88: Perry D, Abraham EP, Baldwin JE (1988). "Factors affecting the isopenicillin N synthetase reaction." Biochem J 255(1);345-51. PMID: 3143358

Raha90: Raha SK, Roy SK, Dey SK, Chakrabarty SL (1990). "Purification and properties of an L-asparaginase from Cylindrocarpon obtusisporum MB-10." Biochem Int 21(6);987-1000. PMID: 2080924

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Saikusa87: Saikusa T, Rhee H, Watanabe K, Murata K, Kimura A (1987). "Metabolism of 2-oxoaldehydes in bacteria: purification and characterization of methylglyoxal reductase from E. coli." Agricultural and Biological Chemistry 51(7): 1893-1899.

Sanchez94: Sanchez JC, Gimenez R, Schneider A, Fessner WD, Baldoma L, Aguilar J, Badia J (1994). "Activation of a cryptic gene encoding a kinase for L-xylulose opens a new pathway for the utilization of L-lyxose by Escherichia coli." J Biol Chem 1994;269(47);29665-9. PMID: 7961955

Uotila74: Uotila L, Koivusalo M (1974). "Purification and properties of S-formylglutathione hydrolase from human liver." J Biol Chem 249(23);7664-72. PMID: 4436331

Yoshida04: Yoshida K, Yamaguchi M, Ikeda H, Omae K, Tsurusaki K, Fujita Y (2004). "The fifth gene of the iol operon of Bacillus subtilis, iolE, encodes 2-keto-myo-inositol dehydratase." Microbiology 150(Pt 3);571-80. PMID: 14993306


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Jan 29, 2015, biocyc14.