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Chemical Compound Review

AGN-PC-00FQZQ     2-amino-4-[[2-[2-[(4-amino-4- carboxy...

Synonyms: HMDB03337, AC1Q5KWQ, AR-1G5850, AKOS015955810, BB_NC-1473, ...
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Disease relevance of glutathione

  • The liver content of total glutathione (32.5 +/- 3.5 nmol GSH eq/mg protein) and GSSG (0.27 +/- 0.09 nmol GSH eq/mg protein) did not change significantly during any period of ischemia or reperfusion [1].
  • Chemically reduced E. coli Trx-(SH)2 was oxidized to Trx-S2 by GSNO with a rate constant of 760 M-1s-1 (7-fold faster than by GSSG) as measured by tryptophan fluorescence [2].
  • Murine L1210 leukemia cells resistant to the antineoplastic agent L-phenylalanine mustard have a 1.5-2.0-fold elevation in their cellular GSH and GSSG content as compared to drug-sensitive cells [3].
  • The rate of GSSG reduction was proportional both to the parasitemia and the hexokinase activity of the lysates [4].
  • Despite this, the MT transgene significantly reduced cardiomyopathy in diabetic mice: OVE26MT hearts showed more normal levels of mRNA and GSSG [5].

Psychiatry related information on glutathione

  • In group A, they were maintained at the low levels until four weeks, whereas they were reversed by resmoking in group B; PDNO release and intraplatelet GSH/GSSG ratio were time-dependently increased by smoking cessation but reversed by resmoking [6].
  • A nocturnal 10-h intracerebroventricular infusion of GSSG significantly enhanced slow wave sleep (SWS) at the dosage range from 20 to 50 nmol and paradoxical sleep (PS) at 25 nmol at the expense of wakefulness during the 12-h dark period [7].
  • Human brain levels of glutathione (GSH), glutathione disulfide (GSSG), and vitamin E were measured in neurologically normal control patients and two groups of patients with neurodegeneration: those with Alzheimer's disease (AD), and AD with some features of Parkinson's disease (AD-PD) [8].
  • Hematological parameters, dietary intake, physical activity intensity, antioxidant status (GSH/GSSG ratio), and basal iron status (serum iron, transferrin, ferritin, and iron saturation index) were determined before and after the intervention trials [9].

High impact information on glutathione

  • Here we demonstrate the absence of glutathione reductase in Drosophila melanogaster, identify a new type of thioredoxin reductase, and provide evidence that a thioredoxin system supports GSSG reduction [10].
  • The pollen NADPH oxidases rapidly increased the levels of ROS in lung epithelium as well as the amount of oxidized glutathione (GSSG) and 4-hydroxynonenal (4-HNE) in airway-lining fluid [11].
  • These oxidases, as well as products of oxidative stress (such as GSSG and 4-HNE) generated by these enzymes, induced neutrophil recruitment to the airways independent of the adaptive immune response [11].
  • These periods of oxidative stress occurred immediately after CO exposure and 120 min after reoxygenation, as indicated by 50 and 43% decreases in GSH/GSSG, respectively [12].
  • Furthermore, in vivo and in vitro data show the equilibration to be catalyzed by glutaredoxins and that conditions of high intracellular GSSG confer to these a new role as dithiol oxidases [13].

Chemical compound and disease context of glutathione


Biological context of glutathione


Anatomical context of glutathione

  • However, neither dsRNA alone nor GSSG alone significantly inhibits formation of [40S subunit-Met-tRNAf] complexes induced in reticulocyte lysates by dsRNA or GSSG involves one or more components present in the lysates but absent from the fractionated in vitro system [22].
  • Glutathione and GSSG form the principle redox buffering system in the cell, with the endoplasmic reticulum (ER) being more oxidizing than the cytoplasm [23].
  • This study demonstrates that changes in endothelial cell GSSG/GSH cause transcription-independent and transcription-dependent surface expression of different endothelial cell adhesion molecules, which leads to a 2-phase neutrophil-endothelial adhesion response [24].
  • This resistance was associated with elevated GSH, NADPH (reduced nicotinamide adenine dinucleotide phosphate), TBH metabolism, redox enzyme activities, reduced cellular GSH/GSSG (glutathione disulfide) status and preservation of mitochondrial membrane potential [25].
  • A progressive decrease of the GSH/GSSG ratio was observed during osteoclast differentiation, and the phenomenon was dependent on a decrease in total glutathione via downregulation of expression of the gamma-glutamylcysteinyl synthetase modifier gene [26].

Associations of glutathione with other chemical compounds


Gene context of glutathione


Analytical, diagnostic and therapeutic context of glutathione

  • No increased GSSG secretion into bile was detectable at any time during reperfusion [1].
  • GSSG and GSH were released from the heart into the effluent perfusion fluid at rates of 110 and 370 pmol X min-1 X g of heart-1, respectively, much lower than for similar conditions in liver [36].
  • We found that plasma allowed to stand at 23 degrees C for 30 to 60 min has total glutathione levels of 4 to 7 microM, most (95%) of which is GSSG; after treatment of this plasma (following deproteinization) with KBH4, levels of 21 to 24 microM were found [37].
  • An improved HPLC measurement for GSH and GSSG in human blood [38].
  • Patients with asthma also had significantly higher GSSG levels in erythrocyte hemolysates compared with controls (167.40 +/- 2.93 micromol/L vs 44.98 +/- 0.44 micromol/L for the asthma and control groups, respectively; P <.001), indicating increased oxidative stress [39].


  1. Reactive oxygen species during ischemia-reflow injury in isolated perfused rat liver. Jaeschke, H., Smith, C.V., Mitchell, J.R. J. Clin. Invest. (1988) [Pubmed]
  2. S-nitrosoglutathione is cleaved by the thioredoxin system with liberation of glutathione and redox regulating nitric oxide. Nikitovic, D., Holmgren, A. J. Biol. Chem. (1996) [Pubmed]
  3. Elevation of glutathione in phenylalanine mustard-resistant murine L1210 leukemia cells. Ahmad, S., Okine, L., Le, B., Najarian, P., Vistica, D.T. J. Biol. Chem. (1987) [Pubmed]
  4. Malarial parasite hexokinase and hexokinase-dependent glutathione reduction in the Plasmodium falciparum-infected human erythrocyte. Roth, E.F. J. Biol. Chem. (1987) [Pubmed]
  5. Overexpression of metallothionein reduces diabetic cardiomyopathy. Liang, Q., Carlson, E.C., Donthi, R.V., Kralik, P.M., Shen, X., Epstein, P.N. Diabetes (2002) [Pubmed]
  6. Only two-week smoking cessation improves platelet aggregability and intraplatelet redox imbalance of long-term smokers. Morita, H., Ikeda, H., Haramaki, N., Eguchi, H., Imaizumi, T. J. Am. Coll. Cardiol. (2005) [Pubmed]
  7. Oxidized glutathione regulates physiological sleep in unrestrained rats. Honda, K., Komoda, Y., Inoué, S. Brain Res. (1994) [Pubmed]
  8. Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. Adams, J.D., Klaidman, L.K., Odunze, I.N., Shen, H.C., Miller, C.A. Mol. Chem. Neuropathol. (1991) [Pubmed]
  9. Antioxidant diet supplementation influences blood iron status in endurance athletes. Aguilo, A., Tauler, P., Fuentespina, E., Villa, G., Cordova, A., Tur, J.A., Pons, A. International journal of sport nutrition and exercise metabolism. (2004) [Pubmed]
  10. Substitution of the thioredoxin system for glutathione reductase in Drosophila melanogaster. Kanzok, S.M., Fechner, A., Bauer, H., Ulschmid, J.K., Müller, H.M., Botella-Munoz, J., Schneuwly, S., Schirmer, R., Becker, K. Science (2001) [Pubmed]
  11. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. Boldogh, I., Bacsi, A., Choudhury, B.K., Dharajiya, N., Alam, R., Hazra, T.K., Mitra, S., Goldblum, R.M., Sur, S. J. Clin. Invest. (2005) [Pubmed]
  12. Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. Zhang, J., Piantadosi, C.A. J. Clin. Invest. (1992) [Pubmed]
  13. Monitoring disulfide bond formation in the eukaryotic cytosol. Østergaard, H., Tachibana, C., Winther, J.R. J. Cell Biol. (2004) [Pubmed]
  14. Oxidative stress and endothelial function in chronic renal failure. Annuk, M., Zilmer, M., Lind, L., Linde, T., Fellström, B. J. Am. Soc. Nephrol. (2001) [Pubmed]
  15. Energy restriction but not protein source affects antioxidant capacity in athletes. Rankin, J.W., Shute, M., Heffron, S.P., Saker, K.E. Free Radic. Biol. Med. (2006) [Pubmed]
  16. Toxicity, single-strand breaks, and 5-hydroxymethyl-2'-deoxyuridine formation in human breast epithelial cells treated with hydrogen peroxide. Djuric, Z., Everett, C.K., Luongo, D.A. Free Radic. Biol. Med. (1993) [Pubmed]
  17. Free radical scavenging and antioxidant activity of allopurinol and oxypurinol in experimental lens-induced uveitis. Augustin, A.J., Böker, T., Blumenröder, S.H., Lutz, J., Spitznas, M. Invest. Ophthalmol. Vis. Sci. (1994) [Pubmed]
  18. Glutathione protects human airway proteins and epithelial cells from isocyanates. Wisnewski, A.V., Liu, Q., Liu, J., Redlich, C.A. Clin. Exp. Allergy (2005) [Pubmed]
  19. Glutathione disulfide-stimulated Mg2+-ATPase of human erythrocyte membranes. Kondo, T., Kawakami, Y., Taniguchi, N., Beutler, E. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  20. Parkinson disease: a new link between monoamine oxidase and mitochondrial electron flow. Cohen, G., Farooqui, R., Kesler, N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  21. Oxidative damage to mitochondrial DNA and glutathione oxidation in apoptosis: studies in vivo and in vitro. Esteve, J.M., Mompo, J., Garcia de la Asuncion, J., Sastre, J., Asensi, M., Boix, J., Vina, J.R., Vina, J., Pallardo, F.V. FASEB J. (1999) [Pubmed]
  22. Inhibition of protein synthesis in rabbit reticulocyte lysates by double-stranded RNA and oxidized glutathione: indirect mode of action on polypeptide chain initiation. Clemens, M.J., Safer, B., Merrick, W.C., Anderson, W.F., London, I.M. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  23. Yeast flavin-containing monooxygenase generates oxidizing equivalents that control protein folding in the endoplasmic reticulum. Suh, J.K., Poulsen, L.L., Ziegler, D.M., Robertus, J.D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  24. Molecular mechanisms of neutrophil-endothelial cell adhesion induced by redox imbalance. Kokura, S., Wolf, R.E., Yoshikawa, T., Granger, D.N., Aw, T.Y. Circ. Res. (1999) [Pubmed]
  25. Decreased susceptibility of differentiated PC12 cells to oxidative challenge: relationship to cellular redox and expression of apoptotic protease activator factor-1. Ekshyyan, O., Aw, T.Y. Cell Death Differ. (2005) [Pubmed]
  26. Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors. Huh, Y.J., Kim, J.M., Kim, H., Song, H., So, H., Lee, S.Y., Kwon, S.B., Kim, H.J., Kim, H.H., Lee, S.H., Choi, Y., Chung, S.C., Jeong, D.W., Min, B.M. Cell Death Differ. (2006) [Pubmed]
  27. Pathways for the reduction of oxidized glutathione in the Plasmodium falciparum-infected erythrocyte: can parasite enzymes replace host red cell glucose-6-phosphate dehydrogenase? Roth, E.F., Schulman, S., Vanderberg, J., Olson, J. Blood (1986) [Pubmed]
  28. Active transport of GSSG from reconstituted erythrocyte ghosts. Prchal, J., Srivastava, S.K., Beutler, E. Blood (1975) [Pubmed]
  29. Role of fatty acyl coenzyme A oxidase in the efflux of oxidized glutathione from perfused livers of rats treated with the peroxisome proliferator nafenopin. Conway, J.G., Neptun, D.A., Garvey, L.K., Popp, J.A. Cancer Res. (1987) [Pubmed]
  30. Early redox imbalance mediates hydroperoxide-induced apoptosis in mitotic competent undifferentiated PC-12 cells. Pias, E.K., Aw, T.Y. Cell Death Differ. (2002) [Pubmed]
  31. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Carlo, M.D., Loeser, R.F. Arthritis Rheum. (2003) [Pubmed]
  32. Acute cadmium exposure inactivates thioltransferase (Glutaredoxin), inhibits intracellular reduction of protein-glutathionyl-mixed disulfides, and initiates apoptosis. Chrestensen, C.A., Starke, D.W., Mieyal, J.J. J. Biol. Chem. (2000) [Pubmed]
  33. Cooperative action of antioxidant defense systems in Drosophila. Missirlis, F., Phillips, J.P., Jäckle, H. Curr. Biol. (2001) [Pubmed]
  34. Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/MRP2. Suzuki, H., Sugiyama, Y. Semin. Liver Dis. (1998) [Pubmed]
  35. Differential oxidation of thioredoxin-1, thioredoxin-2, and glutathione by metal ions. Hansen, J.M., Zhang, H., Jones, D.P. Free Radic. Biol. Med. (2006) [Pubmed]
  36. Cardiac transport of glutathione disulfide and S-conjugate. Studies with isolated perfused rat heart during hydroperoxide metabolism. Ishikawa, T., Sies, H. J. Biol. Chem. (1984) [Pubmed]
  37. Dynamic state of glutathione in blood plasma. Anderson, M.E., Meister, A. J. Biol. Chem. (1980) [Pubmed]
  38. An improved HPLC measurement for GSH and GSSG in human blood. Giustarini, D., Dalle-Donne, I., Colombo, R., Milzani, A., Rossi, R. Free Radic. Biol. Med. (2003) [Pubmed]
  39. Systemic oxidative and antioxidative status in Chinese patients with asthma. Mak, J.C., Leung, H.C., Ho, S.P., Law, B.K., Lam, W.K., Tsang, K.W., Ip, M.S., Chan-Yeung, M. J. Allergy Clin. Immunol. (2004) [Pubmed]
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