|Jmol-3D images||Image 1|
|Molar mass||307.32 g mol−1|
|Melting point||195 °C (383 °F; 468 K)|
|Solubility in water||Freely soluble|
|Solubility in methanol, diethyl ether||Insoluble|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
Glutathione (GSH) is an important antioxidant in plants, animals, fungi and some bacteria and archaea, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side-chain and the amine group of cysteine (which is attached by normal peptide linkage to a glycine).
Thiol groups are reducing agents, existing at a concentration of approximately 5 mM in animal cells. Glutathione reduces disulfide bonds formed within cytoplasmic proteins to cysteines by serving as an electron donor. In the process, glutathione is converted to its oxidized form, glutathione disulfide (GSSG), also called L-(–)-glutathione.
Once oxidized, glutathione can be reduced back by glutathione reductase, using NADPH as an electron donor. The ratio of reduced glutathione to oxidized glutathione within cells is often used as a measure of cellular toxicity.
Glutathione is not an essential nutrient, since it can be synthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine. The sulfhydryl group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of glutathione. Cysteine is the rate-limiting factor in cellular glutathione synthesis, since this amino acid is relatively rare in foodstuffs.
Cells make glutathione in two adenosine triphosphate (ATP)-dependent steps:
- First, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine via the enzyme gamma-glutamylcysteine synthetase (glutamate cysteine ligase, GCL). This reaction is the rate-limiting step in glutathione synthesis.
- Second, glycine is added to the C-terminal of gamma-glutamylcysteine via the enzyme glutathione synthetase.
Animal glutamate cysteine ligase (GCL) is a heterodimeric enzyme composed of a catalytic (GCLC) and modulatory (GCLM) subunit. GCLC constitutes all the enzymatic activity, whereas GCLM increases the catalytic efficiency of GCLC. Mice lacking GCLC (i.e., lacking all de novo GSH synthesis) die before birth. Mice lacking GCLM demonstrate no outward phenotype, but exhibit marked decrease in GSH and increased sensitivity to toxic insults.
While all cells in the human body are capable of synthesizing glutathione, liver glutathione synthesis has been shown to be essential. Mice with genetically-induced loss of GCLC (i.e., GSH synthesis) only in the liver die within 1 month of birth.
The plant glutamate cysteine ligase (GCL) is a redox-sensitive homodimeric enzyme, conserved in the plant kingdom. In an oxidizing environment, intermolecular disulfide bridges are formed and the enzyme switches to the dimeric active state. The midpoint potential of the critical cysteine pair is -318 mV. In addition to the redox-dependent control is the plant GCL enzyme feedback inhibited by GSH. GCL is exclusively located in plastids, and glutathione synthetase is dual-targeted to plastids and cytosol, thus are GSH and gamma-glutamylcysteine exported from the plastids. Both glutathione biosynthesis enzymes are essential in plants; knock-outs of GCL and GS are lethal to embryo and seedling.
The biosynthesis pathway for glutathione is found in some bacteria, like cyanobacteria and proteobacteria, but is missing in many other bacteria. Most eukaryotes synthesize glutathione, including humans, but some do not, such as Leguminosae, Entamoeba, and Giardia. The only archaea that make glutathione are halobacteria.
Glutathione exists in both reduced (GSH) and oxidized (GSSG) states. In the reduced state, the thiol group of cysteine is able to donate a reducing equivalent (H++ e−) to other unstable molecules, such as reactive oxygen species. In donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to form glutathione disulfide (GSSG). Such a reaction is probable due to the relatively high concentration of glutathione in cells (up to 5 mM in the liver).
GSH can be regenerated from GSSG by the enzyme glutathione reductase (GSR): NADPH reduces FAD present in GSR to produce a transient FADH-anion. This anion then quickly breaks a disulfide bond (Cys58 - Cys63) and leads to Cys63's nucleophilically attacking the nearest sulfide unit in the GSSG molecule (promoted by His467), which creates a mixed disulfide bond (GS-Cys58) and a GS-anion. His467 of GSR then protonates the GS-anion to form the first GSH. Next, Cys63 nucleophilically attacks the sulfide of Cys58, releasing a GS-anion, which, in turn, picks up a solvent proton and is released from the enzyme, thereby creating the second GSH. So, for every GSSG and NADPH, two reduced GSH molecules are gained, which can again act as antioxidants scavenging reactive oxygen species in the cell.
In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than 10% exists in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is considered indicative of oxidative stress.
Glutathione has multiple functions:
- It is the major endogenous antioxidant produced by the cells, participating directly in the neutralization of free radicals and reactive oxygen compounds, as well as maintaining exogenous antioxidants such as vitamins C and E in their reduced (active) forms.
- Regulation of the nitric oxide cycle, which is critical for life but can be problematic if unregulated
- It is used in metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Thus, every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system and the lungs.
- It has a vital function in iron metabolism. Yeast cells depleted of or containing toxic levels of GSH show an intense iron starvation-like response and impairment of the activity of extra-mitochondrial ISC enzymes, followed by death.
Function in animals
GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals.
In the case of N-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by paracetamol (or acetaminophen as it is known in the US), which becomes toxic when GSH is depleted by an overdose of acetaminophen, glutathione is an essential antidote to overdose. Glutathione conjugates to NAPQI and helps to detoxify it. In this capacity, it protects cellular protein thiol groups, which would otherwise become covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetyl-L-cysteine (often as a preparation called Mucomyst), which is processed by cells to L-cysteine and used in the de novo synthesis of GSH.
Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. 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 I (EC 220.127.116.11) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-lactoyl-glutathione. Glyoxalase II (EC 18.104.22.168) catalyzes the hydrolysis of S-D-lactoyl-glutathione to glutathione and D-lactic acid.
Glutathione has recently been used as an inhibitor of melanin in the cosmetics industry. In countries like Japan and the Philippines, this product is sold as a skin whitening soap. Glutathione competitively inhibits melanin synthesis in the reaction of tyrosinase and L-DOPA by interrupting L-DOPA's ability to bind to tyrosinase during melanin synthesis. The inhibition of melanin synthesis was reversed by increasing the concentration of L-DOPA, but not by increasing tyrosinase. Although the synthesized melanin was aggregated within one hour, the aggregation was inhibited by the addition of glutathione. These results indicate that glutathione inhibits the synthesis and agglutination of melanin by interrupting the function of L-DOPA."
Function in plants
In plants, glutathione is crucial for biotic and abiotic stress management. It is a pivotal component of the glutathione-ascorbate cycle, a system that reduces poisonous hydrogen peroxide. It is the precursor of phytochelatins, glutathione oligomers that chelate heavy metals such as cadmium. Glutathione is required for efficient defence against plant pathogens such as Pseudomonas syringae and Phytophthora brassicae. APS reductase, an enzyme of the sulfur assimilation pathway uses glutathione as electron donor. Other enzymes using glutathione as substrate are glutaredoxin, these small oxidoreductases are involved in flower development, salicylic acid and plant defence signalling.
Richie et al. published a long-term, randomized, double-blinded, placebo-controlled study that shows for the first time, daily consumption of glutathione is effective at increasing glutathione blood levels. 
In a previous study of acute oral administration, seven healthy subjects were given a very large dose (3 grams) of oral glutathione, Witschi and coworkers found "it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione." Plasma levels of glutathione, cysteine, and glutamate were tested in the plasma after 270 minutes and three out of four of the subjects did have an increase or rise in their glutathione levels. However, it is possible to increase and maintain appropriate glutathione levels by increasing the daily consumption of glutathione rich foods and/or supplements.[non-primary source needed]
Calcitriol (1,25-dihydroxyvitamin D3), the active metabolite of vitamin D3, after being synthesized from calcifediol in the kidney, increases glutathione levels in the brain and appears to be a catalyst for glutathione production. Calcitriol was found to increase GSH levels in rat astrocyte primary cultures on average by 42%, increasing protein concentrations from 29 nmol/mg to 41 nmol/mg, 24 and 48 hours after administration; this effect was reduced to 11%, relative to the control, 96 hours after administration. It takes about ten days for the body to process vitamin D3 into calcitriol.
Other supplements, including N-acetylcysteine, S-adenosylmethionine (SAMe) and whey protein have also been shown to increase cellular glutathione content in persons suffering from a disease-related glutathione deficiency.
Zinc has been shown to have some influence over de novo glutathione synthesis. Furthermore, magnesium has significant influence on glutathione synthesis, it appears to be an essential cofactor.
Once a tumor has been established, elevated levels of glutathione may act to protect cancerous cells by conferring resistance to chemotherapeutic drugs.
Methods to determine glutathione
Reduced glutathione may be visualized using Ellman's reagent or bimane derivates such as monobromobimane. The monobromobimane method is more sensitive. In this procedure, cells are lysed and thiols extracted using a HCl buffer. The thiols are then reduced with dithiothreitol (DTT) and labelled by monobromobimane. Monobromobimane becomes fluorescent after binding to GSH. The thiols are then separated by HPLC and the fluorescence quantified with a fluorescence detector. Bimane may also be used to quantify glutathione in vivo. The quantification is done by confocal laser scanning microscopy after application of the dye to living cells. Another approach, which allows to measure the glutathione redox potential at a high spatial and temporal resolution in living cells is based on redox imaging using the redox-sensitive green fluorescent protein (roGFP) or redox sensitive yellow fluorescent protein (rxYFP)
Importance in winemaking
The content of glutathione in must determines the browning effect during the production of white wine by trapping the caffeoyltartaric acid quinones generated by enzymic oxidation as grape reaction product (GRP).
- Glutathione synthetase deficiency
- Ophthalmic acid
- roGFP, a tool to measure the cellular glutathione redox potential
- Glutathione-ascorbate cycle
- Bacterial glutathione transferase
- Thioredoxin, a cysteine-containing small proteins with very similar functions as reducing agents
- Glutaredoxin, an antioxidant protein that uses reduced glutathione as a cofactor and is reduced nonenzymatically by it
- Merck Index, 11th Edition, 4369
- Pompella, A; Visvikis, A; Paolicchi, A; Tata, V; Casini, AF (2003). "The changing faces of glutathione, a cellular protagonist". Biochemical Pharmacology 66 (8): 1499–503. doi:10.1016/S0006-2952(03)00504-5. PMID 14555227.
- Couto, Narciso; Malys, Naglis; Gaskell, Simon; Barber, Jill (2013). "Partition and Turnover of Glutathione Reductase from Saccharomyces cerevisiae: a Proteomic Approach". Journal of Proteome Research 12 (6): 2885–94. doi:10.1021/pr4001948. PMID 23631642.
- Pastore, Anna; Piemonte, Fiorella; Locatelli, Mattia; Lo Russo, Anna Lo; Gaeta, Laura Maria; Tozzi, Giulia; Federici, Giorgio (2003). "Determination of blood total, reduced, and oxidized glutathione in pediatric subjects". Clinical Chemistry 47 (8): 1467–9. PMID 11468240.
- White, C. C.; Viernes, H.; Krejsa, C. M.; Botta, D.; Kavanagh, T. J. (2003). "Fluorescence-based microtiter plate assay for glutamate–cysteine ligase activity". Analytical Biochemistry 318 (2): 175–180. doi:10.1016/S0003-2697(03)00143-X. PMID 12814619.
- Dalton, T; Dieter, MZ; Yang, Y; Shertzer, HG; Nebert, DW (2000). "Knockout of the Mouse Glutamate Cysteine Ligase Catalytic Subunit (Gclc) Gene: Embryonic Lethal When Homozygous, and Proposed Model for Moderate Glutathione Deficiency When Heterozygous". Biochemical and Biophysical Research Communications 279 (2): 324–9. doi:10.1006/bbrc.2000.3930. PMID 11118286.
- Yang, Y.; Dieter, MZ; Chen, Y; Shertzer, HG; Nebert, DW; Dalton, TP (2002). "Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(-/-) knockout mouse. Novel model system for a severely compromised oxidative stress response". Journal of Biological Chemistry 277 (51): 49446–52. doi:10.1074/jbc.M209372200. PMID 12384496.
- Giordano, G; Afsharinejad, Z; Guizzetti, M; Vitalone, A; Kavanagh, T; Costa, L (2007). "Organophosphorus insecticides chlorpyrifos and diazinon and oxidative stress in neuronal cells in a genetic model of glutathione deficiency". Toxicology and Applied Pharmacology 219 (2–3): 181–9. doi:10.1016/j.taap.2006.09.016. PMID 17084875.
- McConnachie, L. A.; Mohar, I.; Hudson, F. N.; Ware, C. B.; Ladiges, W. C.; Fernandez, C.; Chatterton-Kirchmeier, S.; White, C. C.; Pierce, R. H.; Kavanagh, T. J. (2007). "Glutamate Cysteine Ligase Modifier Subunit Deficiency and Gender as Determinants of Acetaminophen-Induced Hepatotoxicity in Mice". Toxicological Sciences 99 (2): 628–36. doi:10.1093/toxsci/kfm165. PMID 17584759.
- Chen, Ying; Yang, Yi; Miller, Marian L.; Shen, Dongxiao; Shertzer, Howard G.; Stringer, Keith F.; Wang, Bin; Schneider, Scott N.; Nebert, Daniel W.; Dalton, Timothy P. (2007). "Hepatocyte-specificGclcdeletion leads to rapid onset of steatosis with mitochondrial injury and liver failure". Hepatology 45 (5): 1118–28. doi:10.1002/hep.21635. PMID 17464988.
- Hothorn, M.; Wachter, A; Gromes, R; Stuwe, T; Rausch, T; Scheffzek, K (2006). "Structural Basis for the Redox Control of Plant Glutamate Cysteine Ligase". Journal of Biological Chemistry 281 (37): 27557–65. doi:10.1074/jbc.M602770200. PMID 16766527.
- Hicks, L. M.; Cahoon, R. E.; Bonner, E. R.; Rivard, R. S.; Sheffield, J.; Jez, J. M. (2007). "Thiol-Based Regulation of Redox-Active Glutamate-Cysteine Ligase from Arabidopsis thaliana". The Plant Cell Online 19 (8): 2653–61. doi:10.1105/tpc.107.052597. PMC 2002632. PMID 17766407.
- Wachter, Andreas; Wolf, Sebastian; Steininger, Heike; Bogs, Jochen; Rausch, Thomas (2004). "Differential targeting of GSH1 and GSH2 is achieved by multiple transcription initiation: implications for the compartmentation of glutathione biosynthesis in the Brassicaceae". The Plant Journal 41 (1): 15–30. doi:10.1111/j.1365-313X.2004.02269.x. PMID 15610346.
- Pasternak, Maciej; Lim, Benson; Wirtz, Markus; Hell, RüDiger; Cobbett, Christopher S.; Meyer, Andreas J. (2007). "Restricting glutathione biosynthesis to the cytosol is sufficient for normal plant development". The Plant Journal 53 (6): 999–1012. doi:10.1111/j.1365-313X.2007.03389.x. PMID 18088327.
- Copley, Shelley D; Dhillon, Jasvinder K (2002). Genome Biology 3 (5): research0025.1. doi:10.1186/gb-2002-3-5-research0025.
- Grill D, Tausz T, De Kok LJ (2001). Significance of glutathione in plant adaptation to the environment. Springer. ISBN 1-4020-0178-9.
- Halprin, Kenneth (1967). "The Measurement of Glutathione in Human Epidermis using Glutathione Reductase". Journal of Investigative Dermatology 48 (2): 149.
- Scholz RW. Graham KS. Gumpricht E. Reddy CC. Mechanism of interaction of vitamin E and glutathione in the protection against membrane lipid peroxidation. Ann NY Acad Sci 1989:570:514-7. Hughes RE. Reduction of dehydroascorbic acid by animal tissues. Nature 1964:203:1068-9.
- Clementi, Emilio; Smith, Guy Charles; Howden, Martin; Dietrich, Salvador; Bugg, S; O'Connell, MJ; Goldsbrough, PB; Cobbett, CS (1999). "Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe". The Plant cell 11 (6): 1153–64. doi:10.1105/tpc.11.6.1153. JSTOR 3870806. PMC 144235. PMID 10368185.
- Chitranshu Kumar et al. Glutathione revisited: a vital function in iron metabolism and ancillary role in thiol-redox control. The EMBO Journal (2011) 30, 2044–2056 doi:10.1038/emboj.2011.105
- "Pharmaceutical Information - MUCOMYST". RxMed. Retrieved 2014-02-13.
- Matsuki, Mitsuo; Watanabe, Toshihiko; Ogasawara, Ayako; Mikami, Takeshi; Matsumoto, Tatsuji (2008). "Inhibitory Mechanism of Melanin Synthesis by Glutathione". Yakugaku Zasshi 128 (8): 1203–7. doi:10.1248/yakushi.128.1203. PMID 18670186.
- Noctor, Graham; Foyer, Christine H. (1998). "ASCORBATE AND GLUTATHIONE: Keeping Active Oxygen Under Control". Annual Review of Plant Physiology and Plant Molecular Biology 49: 249–279. doi:10.1146/annurev.arplant.49.1.249. PMID 15012235.
- Ha, S.-B.; Smith, AP; Howden, R; Dietrich, WM; Bugg, S; O'Connell, MJ; Goldsbrough, PB; Cobbett, CS (1999). "Phytochelatin Synthase Genes from Arabidopsis and the Yeast Schizosaccharomyces pombe". The Plant Cell Online 11 (6): 1153–64. doi:10.1105/tpc.11.6.1153. PMC 144235. PMID 10368185.
- Parisy, Vincent; Poinssot, Benoit; Owsianowski, Lucas; Buchala, Antony; Glazebrook, Jane; Mauch, Felix (2006). "Identification of PAD2 as a γ-glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis". The Plant Journal 49 (1): 159–72. doi:10.1111/j.1365-313X.2006.02938.x. PMID 17144898.
- Rouhier, Nicolas; Lemaire, StéPhane D.; Jacquot, Jean-Pierre (2008). "The Role of Glutathione in Photosynthetic Organisms: Emerging Functions for Glutaredoxins and Glutathionylation". Annual Review of Plant Biology 59: 143–66. doi:10.1146/annurev.arplant.59.032607.092811. PMID 18444899.
- Richie Jr, J.P.; Nichenametla, S.; Neidig, W.; Calcagnotto, A.; Haley, JS; Schell, T.D.; Muscat, J.E. (2014). "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione". European Journal of Nutrition. doi:10.1007/s00394-014-0706-z. PMID 24791752.
- Witschi, A.; Reddy, S.; Stofer, B.; Lauterburg, B. H. (1992). "The systemic availability of oral glutathione". European Journal of Clinical Pharmacology 43 (6): 667–9. doi:10.1007/BF02284971. PMID 1362956.
- Lands, L. C.; Grey, V. L.; Smountas, A. A. (1999). "Effect of supplementation with a cysteine donor on muscular performance". Journal of applied physiology (Bethesda, Md. : 1985) 87 (4): 1381–1385. PMID 10517767.
- Garcion, E; Wion-Barbot, N; Montero-Menei, C; Berger, F; Wion, D (2002). "New clues about vitamin D functions in the nervous system". Trends in Endocrinology and Metabolism 13 (3): 100–5. doi:10.1016/S1043-2760(01)00547-1. PMID 11893522.
- Garcion, E.; Sindji, L.; Leblondel, G.; Brachet, P.; Darcy, F. (2002). "1,25-Dihydroxyvitamin D3 Regulates the Synthesis of γ-Glutamyl Transpeptidase and Glutathione Levels in Rat Primary Astrocytes". Journal of Neurochemistry 73 (2): 859–866. doi:10.1046/j.1471-4159.1999.0730859.x. PMID 10428085.
- Van Groningen, L.; Opdenoordt, S.; Van Sorge, A.; Telting, D.; Giesen, A.; De Boer, H. (2010). "Cholecalciferol loading dose guideline for vitamin D-deficient adults". European Journal of Endocrinology 162 (4): 805–811. doi:10.1530/EJE-09-0932. PMID 20139241.
- Meyer, Alain (1994). "The effect of oral N-acetylcysteine on lung glutathione levels in idiopathic pulmonary fibrosis". European Respirotory Journal 7 (3): 431–436. doi:10.1183/09031936.94.07030431. PMID 8013597.
- Lieber, Charles S. (2002). "S-adenosyl-L-methionine: its role in the treatment of liver disorders". The American journal of clinical nutrition 76 (5): 1183S–7S. PMID 12418503.
- Vendemiale, G.; Altomare, E.; Trizio, T.; Le Grazie, C.; Di Padova, C.; Salerno, M. T.; Carrieri, V.; Albano, O. (1989). "Effects of Oral S-Adenosyl-l-Methionine on Hepatic Glutathione in Patients with Liver Disease". Scandinavian Journal of Gastroenterology 24 (4): 407–15. doi:10.3109/00365528909093067. PMID 2781235.
- Loguercio, C; Nardi, G; Argenzio, F; Aurilio, C; Petrone, E; Grella, A; Del Vecchio Blanco, C; Coltorti, M (1994). "Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease". Alcohol and alcoholism (Oxford, Oxfordshire) 29 (5): 597–604. PMID 7811344.
- Micke, P.; Beeh, K. M.; Schlaak, J. F.; Buhl, R. (2001). "Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients". European Journal of Clinical Investigation 31 (2): 171–8. doi:10.1046/j.1365-2362.2001.00781.x. PMID 11168457.
- Moreno, Y. F.; Sgarbieri, VC; Da Silva, MN; Toro, AA; Vilela, MM (2006). "Features of Whey Protein Concentrate Supplementation in Children with Rapidly Progressive HIV Infection". Journal of Tropical Pediatrics 52 (1): 34–8. doi:10.1093/tropej/fmi074. PMID 16014759.
- Grey, V; Mohammed, SR; Smountas, AA; Bahlool, R; Lands, LC (2003). "Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein". Journal of Cystic Fibrosis 2 (4): 195–8. doi:10.1016/S1569-1993(03)00097-3. PMID 15463873.
- Micke, P.; Beeh, K. M.; Buhl, R. (2002). "Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients". European Journal of Nutrition 41 (1): 12–8. doi:10.1007/s003940200001. PMID 11990003.
- Ha, K. -N. (2006). "Increased Glutathione Synthesis through an ARE-Nrf2-Dependent Pathway by Zinc in the RPE: Implication for Protection against Oxidative Stress". Investigative Ophthalmology & Visual Science 47 (6): 2709. doi:10.1167/iovs.05-1322.
- Omata, Y.; Salvador, G. A.; Supasai, S.; Keenan, A. H.; Oteiza, P. I. (2013). "Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain". Toxicological Sciences 133 (1): 90–100. doi:10.1093/toxsci/kft022. PMC 3627551. PMID 23377617.
- Mills, B. J.; Lindeman, R. D.; Lang, C. A. (1981). "Effect of zinc deficiency on blood glutathione levels". The Journal of nutrition 111 (6): 1098–102. PMID 7241230.
- Mills, B. J.; Lindeman, R. D.; Lang, C. A. (1986). "Magnesium deficiency inhibits biosynthesis of blood glutathione and tumor growth in the rat". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 181 (3): 326–32. PMID 3945642.
- Hsu, J. M.; Rubenstein, B; Paleker, A. G. (1982). "Role of magnesium in glutathione metabolism of rat erythrocytes". The Journal of nutrition 112 (3): 488–96. PMID 7062145.
- Barbagallo, M; Dominguez, L. J.; Tagliamonte, M. R.; Resnick, L. M.; Paolisso, G (1999). "Effects of glutathione on red blood cell intracellular magnesium: Relation to glucose metabolism". Hypertension 34 (1): 76–82. doi:10.1161/01.hyp.34.1.76. PMID 10406827.
- Bede; Nagy (2008). "Effects of magnesium supplementation on the glutathione redox system in atopic asthmatic children". Inflammation Research 57 (6): 279–86. PMID 18516713.
- Regan, R. F.; Guo, Y (2001). "Magnesium deprivation decreases cellular reduced glutathione and causes oxidative neuronal death in murine cortical cultures". Brain research 890 (1): 177–83. PMID 11164781.
- Dröge, Wulf; Holm, Eggert (1997). "Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction". The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 (13): 1077–89. PMID 9367343.
- Balendiran, Ganesaratnam K.; Dabur, Rajesh; Fraser, Deborah (2004). "The role of glutathione in cancer". Cell Biochemistry and Function 22 (6): 343–52. doi:10.1002/cbf.1149. PMID 15386533.
- Meyer, Andreas J.; May, Mike J.; Fricker, Mark (2001). "Quantitative in vivo measurement of glutathione in Arabidopsis cells". The Plant Journal 27 (1): 67–78. doi:10.1046/j.1365-313x.2001.01071.x. PMID 11489184.
- Meyer, Andreas J.; Brach, Thorsten; Marty, Laurent; Kreye, Susanne; Rouhier, Nicolas; Jacquot, Jean-Pierre; Hell, RüDiger (2007). "Redox-sensitive GFP inArabidopsis thalianais a quantitative biosensor for the redox potential of the cellular glutathione redox buffer". The Plant Journal 52 (5): 973–86. doi:10.1111/j.1365-313X.2007.03280.x. PMID 17892447.
- Maulucci, Giuseppe; Labate, Valentina; Mele, Marina; Panieri, Emiliano; Arcovito, Giuseppe; Galeotti, Tommaso; Østergaard, H; Winther, JR; De Spirito, Marco; Pani, G. (2008). "High-resolution imaging of redox signaling in live cells through an oxidation-sensitive yellow fluorescent protein". Science Signaling 1 (43): pl3. doi:10.1126/scisignal.143pl3. PMID 18957692.
- Influence of must composition on phenolic oxidation kinetics. Jacques Rigaud, Véronique Cheynier, Jean-Marc Souquet and Michel Moutounet, Journal of the Science of Food and Agriculture, 1991, Volume 57, Issue 1, pages 55–63, doi:10.1002/jsfa.2740570107
- Drevet, J (2006). "The antioxidant glutathione peroxidase family and spermatozoa: A complex story". Molecular and Cellular Endocrinology 250 (1–2): 70–9. doi:10.1016/j.mce.2005.12.027. PMID 16427183.
- Wu, Guoyao; Fang, Yun-Zhong; Yang, Sheng; Lupton, Joanne R.; Turner, Nancy D. (2004). "Glutathione metabolism and its implications for health". The Journal of nutrition 134 (3): 489–92. PMID 14988435.