Figure 1The “Glutathione Pathway”

The figure shows a schematic representation of the “glutathione pathway.” Glutathione (GSH) is synthesized from glutamate, cysteine, and glycine by γ-glutamylcysteine synthetase and glutathione synthetase. Glutathione redox state is regulated, in part, by glutathione peroxidases, forming oxidized glutathione (GSSG), and by a reaction catalyzed by glutathione reductase. Glutathione is conjugated to substrates both through the action of the glutathione S-transferases and through non-enzymatic reactions. Glutathione conjugates can be excreted from the cells by members of the ABCC transporter family.

Glutathione Pathway Genetic Polymorphisms and Lung Cancer Survival After Platinum-Based Chemotherapy

Cancer Epidemiol Biomarkers Prev. 2010 March;19(3):811-821.
Figure 1Glutathione monoethyl ester but not glutathione elevates intracellular glutathione levels

Mesencephalic cultures were preloaded for 24hr with either the monoethyl ester of glutathione (A) or with reduced glutathione (B).(C) Some cultures had glutathione partially depleted prior to loading by treatment for 24hr with buthionine sulfoximine (BSO, 1μM). GEE loading was carried out in the presence or absence of BSO. Following loading, cultures were washed, intracellular content extracted and glutathione quantified by HPLC. The n is from 4–5 separate experiments run in duplicate. *Different from zero GEE addition.

Characterization of intracellular elevation of glutathione (GSH) with glutathione monoethyl ester and GSH in brain and neuronal cultures: Relevance to Parkinson's disease

Exp Neurol. 2007 February;203(2):512-520.
Figure 6HPLC and LC/MS analysis of the formation of 17DMAG glutathione conjugates

17DMAG glutathione conjugate formation was detected by HPLC and LC-MS. Reaction conditions: 50 μM 17DMAG, 500 μM NADH and 5 mM glutathione in the absence and presence of 11.8 μg rhNQO1 and in the absence or presence of 2 μM ES936, were incubated in 50 mM potassium phosphate buffer (pH 7.4, 1 ml) at room temperature for 3 h. 17DMAG glutathione conjugate formation was analyzed by HPLC at 270 nm (3 h). Panel A, 17DMAG and glutathione; panel B, 17DMAG, NADH, rhNQO1 and glutathione; panel C, 17DMAG, NADH, rhNQO1, ES936 and glutathione; Panel D, LC-MS confirmed 17DMAG-SG as the product of the interaction of 17DMAG and glutathione.

Enzymatic reduction and glutathione conjugation of benzoquinone ansamycin Hsp90 inhibitors: Relevance for toxicity and mechanism of action

Drug Metab Dispos. 2008 October;36(10):2050-2057.
Figure 2Effect of farnesol on intracellular glutathione levels and viability in CA and cdr1 in the presence and absence of exogenous glutathione following 3 h and 18 h exposure to increasing farnesol concentrations.

(A) Significant decrease in glutathione levels in CA proportional to farnesol concentration and time of exposure with minimal decrease in glutathione in cdr1. Exogenous glutathione (G) inhibited drop in intracellular levels in both strains. Error bars indicate the standard errors of the means. (B) Farnesol concentration and exposure time-dependent killing of C. albicans with cdr1 exhibiting decreased susceptibility. However, no killing was observed upon supplementation with exogenous glutathione (G). Error bars indicate the standard errors of the means.

Farnesol-Induced Apoptosis in Candida albicans Is Mediated by Cdr1-p Extrusion and Depletion of Intracellular Glutathione

PLoS One. 2011;6(12):e28830.

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Glutathione metabolism and its implications for health. [J Nutr. 2004]
Glutathione metabolism and its implications for health.
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. J Nutr. 2004 Mar; 134(3):489-92.
The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. [Crit Rev Biochem Mol Biol. 1995]
The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.
Hayes JD, Pulford DJ. Crit Rev Biochem Mol Biol. 1995; 30(6):445-600.
The glutathione peroxidases. [Cell Mol Life Sci. 2000]
The glutathione peroxidases.
Arthur JR. Cell Mol Life Sci. 2000 Dec; 57(13-14):1825-35.

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Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats. [World J Gastroenterol. 2013]
Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats.
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The Redox State of Cytochrome C Modulates Resistance to Methotrexate in Human MCF7 Breast Cancer Cells.
Barros S, Mencia N, Rodríguez L, Oleaga C, Santos C, Noé V, Ciudad CJ. PLoS One. 2013; 8(5):e63276. Epub 2013 May 13.
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Melatonin attenuates high fat diet-induced fatty liver disease in rats.
Hatzis G, Ziakas P, Kavantzas N, Triantafyllou A, Sigalas P, Andreadou I, Ioannidis K, Chatzis S, Filis K, Papalampros A, et al. World J Hepatol. 2013 Apr 27; 5(4):160-9.

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