3D model (JSmol)
CompTox Dashboard (EPA)
|Molar mass||307.32 g·mol−1|
|Melting point||195 °C (383 °F; 468 K)|
|Solubility in methanol, diethyl ether||Insoluble|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
Glutathione (GSH) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine.
Biosynthesis and occurrence
Glutathione biosynthesis involves two adenosine triphosphate-dependent steps:
- First, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine. This conversion requires the enzyme glutamate–cysteine ligase (GCL, glutamate cysteine synthase). This reaction is the rate-limiting step in glutathione synthesis.
- Second, glycine is added to the C-terminal of gamma-glutamylcysteine. This condensation is catalyzed by glutathione synthetase.
While all animal cells are capable of synthesizing glutathione, glutathione synthesis in the liver has been shown to be essential. GCLC knockout mice die within a month of birth due to the absence of hepatic GSH synthesis.
The unusual gamma amide linkage in glutathione protects it from hydrolysis by peptidases.
Glutathione is the most abundant thiol in animal cells, ranging from 0.5 to 10 mM. It is present both in the cytosol and the organelles.
Humans synthesize glutathione, but a few eukaryotes do not, including Leguminosae, Entamoeba, and Giardia. The only archaea that make glutathione are halobacteria. Some bacteria, such as cyanobacteria and proteobacteria, can biosynthesize glutathione.
Glutathione exists in reduced (GSH) and oxidized (GSSG) states. The ratio of reduced glutathione to oxidized glutathione within cells is a measure of cellular oxidative stress. In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH), with the remainder in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is indicative of oxidative stress.
In the reduced state, the thiol group of cysteinyl residue is a source of one reducing equivalent. Glutathione disulfide (GSSG) is thereby generated. The oxidized state is converted to the reduced state by NADPH. This conversion is catalyzed by glutathione reductase:
- NADPH + GSSG + H2O → 2 GSH + NADP+ + OH-
As an antioxidant
- 2 GSH + R2O2 → GSSG + 2 ROH (R = H, alkyl)
and with free radicals:
- GSH + R. → 0.5 GSSG + RH
Aside from deactivating radicals and reactive oxidants, glutathione participates in thiol protection and redox regulation of cellular thiol proteins under oxidative stress by protein S-glutathionylation, a redox-regulated post-translational thiol modification. The general reaction involves formation of an unsymmetrical disulfide from the protectable protein (RSH) and GSH:
- RSH + GSH + [O] → GSSR + H2O
Glutathione is also employed for the detoxification of methylglyoxal and formaldehyde, toxic metabolites produced under oxidative stress. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 184.108.40.206) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-lactoyl-glutathione. Glyoxalase II (EC 220.127.116.11) catalyzes the hydrolysis of S-D-lactoyl-glutathione to glutathione and D-lactic acid.
Among the many metabolic processes in which it participates, glutathione is required for the biosynthesis of leukotriene and prostaglandins. It plays a role in the storage of cysteine. Glutathione enhances the function of citrulline as part of the nitric oxide cycle. It is a cofactor and acts on glutathione peroxidase.
Glutathione facilitates metabolism of xenobiotics. Glutathione S-transferase enzymes catalyze its conjugation to lipophilic xenobiotics, facilitating their excretion or further metabolism. The conjugation process is illustrated by the metabolism of N-acetyl-p-benzoquinone imine (NAPQI). NAPQI is a reactive metabolite formed by the action of cytochrome P450 on paracetamol (acetaminophen). Glutathione conjugates to NAPQI, and the resulting ensemble is excreted.
Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties). GSH and GSSG may be neuromodulators. At millimolar concentrations, GSH and GSSG may also modulate the redox state of the NMDA receptor complex. Glutathione binds and activate ionotropic receptors, potentially making it a neurotransmitter.
In plants, glutathione is involved in stress management. It is a 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. Adenylyl-sulfate reductase, an enzyme of the sulfur assimilation pathway, uses glutathione as an electron donor. Other enzymes using glutathione as a substrate are glutaredoxins. These small oxidoreductases are involved in flower development, salicylic acid, and plant defence signalling.
Bioavailability and supplementation
Systemic bioavailability of orally consumed glutathione is poor because the tripeptide is the substrate of proteases (peptidases) of the alimentary canal, and due to the absence of a specific carrier of glutathione at the level of cell membrane.
Because direct supplementation of glutathione is not always successful, supply of the raw nutritional materials used to generate GSH, such as cysteine and glycine, may be more effective at increasing glutathione levels. Other antioxidants such as ascorbic acid (vitamin C) may also work synergistically with glutathione, preventing depletion of either. The glutathione-ascorbate cycle, which works to detoxify hydrogen peroxide (H2O2), is one very specific example of this phenomenon.
Additionally, compounds such as N-acetylcysteine (NAC) and alpha lipoic acid (ALA, not to be confused with the unrelated alpha-linolenic acid) are both capable of helping to regenerate glutathione levels. NAC in particular is commonly used to treat overdose of acetaminophen, a type of potentially fatal poisoning which is harmful in part due to severe depletion of glutathione levels. It is a precursor of cysteine.
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. About ten days are needed for the body to process vitamin D3 into calcitriol.
S-adenosylmethionine (SAMe), a cosubstrate involved in methyl group transfer, has also been shown to increase cellular glutathione content in persons suffering from a disease-related glutathione deficiency.
Low glutathione is commonly observed in wasting and negative nitrogen balance, as seen in cancer, HIV/AIDS, sepsis, trauma, burns, and athletic overtraining. Low levels are also observed in periods of starvation. These effects are hypothesized to be influenced by the higher glycolytic activity associated with cachexia, which result from reduced levels of oxidative phosphorylation.
Determination of glutathione
Ellman's reagent and monobromobimane
Reduced glutathione may be visualized using Ellman's reagent or bimane derivatives 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 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.
Using monochlorobimane, the quantification is done by confocal laser scanning microscopy after application of the dye to living cells. This quantification process relies on measuring the rates of fluorescence changes and is limited to plant cells.
CMFDA has also been mistakenly used as a glutathione probe. Unlike monochlorobimane, whose fluorescence increases upon reacting with glutathione, the fluorescence increase of CMFDA is due to the hydrolysis of the acetate groups inside cells. Although CMFDA may react with glutathione in cells, the fluorescence increase does not reflect the reaction. Therefore, studies using CMFDA as a glutathione probe should be revisited and reinterpreted.
The major limitation of these bimane-based probes and many other reported probes is that these probes are based on irreversible chemical reactions with glutathione, which renders these probes incapable of monitoring the real-time glutathione dynamics. Recently, the first reversible reaction based fluorescent probe-ThiolQuant Green (TQG)-for glutathione was reported. ThiolQuant Green can not only perform high resolution measurements of glutathione levels in single cells using a confocal microscope, but also be applied in flow cytometry to perform bulk measurements.
The RealThiol (RT) probe is a second-generation reversible reaction-based GSH probe. A few key features of RealThiol: 1) it has a much faster forward and backward reaction kinetics compared to ThiolQuant Green, which enables real-time monitoring of GSH dynamics in live cells; 2) only micromolar to sub-micromolar RealThiol is needed for staining in cell-based experiments, which induces minimal perturbation to GSH level in cells; 3) a high-quantum-yield coumarin fluorophore was implemented so that background noise can be minimized; and 4) equilibrium constant of the reaction between RealThiol and GSH has been fine-tuned to respond to physiologically relevant concentration of GSH. RealThiol can be used to perform measurements of glutathione levels in single cells using a high-resolution confocal microscope, as well as be applied in flow cytometry to perform bulk measurements in high throughput manner.
Organelle-targeted RT probe has also been developed. A mitochondria targeted version, MitoRT, was reported and demonstrated in monitoring the dynamic of mitochondrial glutathione both on confocoal microscope and FACS based analysis.
Protein-based glutathione probes
Another approach, which allows measurement of 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). Because its very low physiological concentration, GSSG is difficult to measure accurately. GSSG concentration ranges from 10 to 50 μM in all solid tissues, and from 2 to 5 μM in blood (13–33 nmol per gram Hb). GSH-to-GSSG ratio of whole cell extracts is estimated from 100 to 700. Those ratios represent a mixture from the glutathione pools of different redox states from different subcellular compartments (e.g. more oxidized in the ER, more reduced in the mitochondrial matrix), however. In vivo GSH-to-GSSG ratios can be measured with subcellular accuracy using fluorescent protein-based redox sensors, which have revealed ratios from 50,000 to 500,000 in the cytosol, which implies that GSSG concentration is maintained in the pM range.
Other biological implications
The sulfur-rich aspect of glutathione results in it forming relatively strong complexes with lead(II).
Once a tumor has been established, elevated levels of glutathione may act to protect cancerous cells by conferring resistance to chemotherapeutic drugs. The antineoplastic mustard drug canfosfamide was modelled on the structure of glutathione.
While extracellular amyloid beta (Aβ) plaques, neurofibrillary tangles (NFT), inflammation in the form of reactive astrocytes and microglia, and neuronal loss are all consistent pathological features of Alzheimer's disease (AD), a mechanistic link between these factors is yet to be clarified. Although the majority of past research has focused on fibrillar Aβ, soluble oligomeric Aβ species are now considered to be of major pathological importance in AD. Upregulation of GSH may be protective against the oxidative and neurotoxic effects of oligomeric Aβ.[medical citation needed]
The content of glutathione in must, the first raw form of wine, determines the browning, or caramelizing effect, during the production of white wine by trapping the caffeoyltartaric acid quinones generated by enzymic oxidation as grape reaction product. Its concentration in wine can be determined by UPLC-MRM mass spectrometry.
Glutathione is the most common agent taken by mouth in an attempt to whiten the skin. It may also be used as a cream. Whether or not it actually works is unclear as of 2019. Due to side effects that may result with intravenous use, the government of the Philippines recommends against such use.
- Reductive stress
- 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
- Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. p. 3.284. ISBN 9781498754293.
- Pompella A, Visvikis A, Paolicchi A, De Tata V, Casini AF (October 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.
- White CC, Viernes H, Krejsa CM, Botta D, Kavanagh TJ (July 2003). "Fluorescence-based microtiter plate assay for glutamate-cysteine ligase activity". Analytical Biochemistry. 318 (2): 175–80. doi:10.1016/S0003-2697(03)00143-X. PMID 12814619.
- Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, Stringer KF, Wang B, Schneider SN, Nebert DW, Dalton TP (May 2007). "Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure". Hepatology. 45 (5): 1118–28. doi:10.1002/hep.21635. PMID 17464988.
- Sies H (1999). "Glutathione and its role in cellular functions". Free Radical Biology & Medicine. 27 (9–10): 916–21. doi:10.1016/S0891-5849(99)00177-X. PMID 10569624.
- Guoyao Wu, Yun-Zhong Fang, Sheng Yang, Joanne R. Lupton, Nancy D. Turner (2004). "Glutathione Metabolism and its Implications for Health". Journal of Nutrition. 134 (3): 489–92. doi:10.1093/jn/134.3.489. PMID 14988435.CS1 maint: multiple names: authors list (link)
- Copley SD, Dhillon JK (29 April 2002). "Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes". Genome Biology. 3 (5): research0025. doi:10.1186/gb-2002-3-5-research0025. PMC 115227. PMID 12049666.
- Wonisch W, Schaur RJ (2001). "Chapter 2: Chemistry of Glutathione". In Grill D, Tausz T, De Kok L (eds.). Significance of glutathione in plant adaptation to the environment. Springer. ISBN 978-1-4020-0178-9 – via Google Books.
- Pastore A, Piemonte F, Locatelli M, Lo Russo A, Gaeta LM, Tozzi G, Federici G (August 2001). "Determination of blood total, reduced, and oxidized glutathione in pediatric subjects". Clinical Chemistry. 47 (8): 1467–9. PMID 11468240.
- Lu SC (May 2013). "Glutathione synthesis". Biochimica et Biophysica Acta. 1830 (5): 3143–53. doi:10.1016/j.bbagen.2012.09.008. PMC 3549305. PMID 22995213.
- Halprin KM, Ohkawara A (1967). "The measurement of glutathione in human epidermis using glutathione reductase". The Journal of Investigative Dermatology. 48 (2): 149–52. doi:10.1038/jid.1967.24. PMID 6020678.
- Couto N, Malys N, Gaskell SJ, Barber J (June 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.
- Michael Brownlee (2005). "The pathobiology of diabetic complications: A unifying mechanism". Diabetes. 54 (6): 1615–25. doi:10.2337/diabetes.54.6.1615. PMID 15919781.
- Dalle-Donne, Isabella; Rossi, Ranieri; Colombo, Graziano; Giustarini, Daniela; Milzani, Aldo (2009). "Protein S-glutathionylation: a regulatory device from bacteria to humans". Trends in Biochemical Sciences. 34 (2): 85–96. doi:10.1016/j.tibs.2008.11.002. PMID 19135374.CS1 maint: multiple names: authors list (link)
- Dringen R (December 2000). "Metabolism and functions of glutathione in brain". Progress in Neurobiology. 62 (6): 649–71. doi:10.1016/s0301-0082(99)00060-x. PMID 10880854.
- Scholz, RW. Graham KS. Gumpricht E. Reddy CC. (1989). "Mechanism of interaction of vitamin E and glutathione in the protection against membrane lipid peroxidation". Ann NY Acad Sci. 570 (1): 514–7. Bibcode:1989NYASA.570..514S. doi:10.1111/j.1749-6632.1989.tb14973.x.
- Hughes RE (1964). "Reduction of dehydroascorbic acid by animal tissues". Nature. 203 (4949): 1068–9. Bibcode:1964Natur.203.1068H. doi:10.1038/2031068a0. PMID 14223080.
- Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS (June 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.
- Grant CM (2001). "Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions". Molecular Microbiology. 39 (3): 533–41. doi:10.1046/j.1365-2958.2001.02283.x. PMID 11169096.
- Hayes, John D.; Flanagan, Jack U.; Jowsey, Ian R. (2005). "Glutathione transferases". Annual Review of Pharmacology and Toxicology. 45: 51–88. doi:10.1146/annurev.pharmtox.45.120403.095857. PMID 15822171.CS1 maint: multiple names: authors list (link)
- Steullet P, Neijt HC, Cuénod M, Do KQ (February 2006). "Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: relevance to schizophrenia". Neuroscience. 137 (3): 807–19. doi:10.1016/j.neuroscience.2005.10.014. PMID 16330153.
- Varga V, Jenei Z, Janáky R, Saransaari P, Oja SS (September 1997). "Glutathione is an endogenous ligand of rat brain N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors". Neurochemical Research. 22 (9): 1165–71. doi:10.1023/A:1027377605054. PMID 9251108.
- Janáky R, Ogita K, Pasqualotto BA, Bains JS, Oja SS, Yoneda Y, Shaw CA (September 1999). "Glutathione and signal transduction in the mammalian CNS". Journal of Neurochemistry. 73 (3): 889–902. doi:10.1046/j.1471-4159.1999.0730889.x. PMID 10461878.
- Oja SS, Janáky R, Varga V, Saransaari P (2000). "Modulation of glutamate receptor functions by glutathione". Neurochemistry International. 37 (2–3): 299–306. doi:10.1016/S0197-0186(00)00031-0. PMID 10812215.
- Freitas HR, Ferraz G, Ferreira GC, Ribeiro-Resende VT, Chiarini LB, do Nascimento JL, Matos Oliveira KR, Pereira Tde L, Ferreira LG, Kubrusly RC, Faria RX, Herculano AM, Reis RA (14 April 2016). "Glutathione-Induced Calcium Shifts in Chick Retinal Glial Cells". PLOS ONE. 11 (4): e0153677. Bibcode:2016PLoSO..1153677F. doi:10.1371/journal.pone.0153677. PMC 4831842. PMID 27078878.
- Freitas HR, Reis RA (1 January 2017). "Glutathione induces GABA release through P2X7R activation on Müller glia". Neurogenesis. 4 (1): e1283188. doi:10.1080/23262133.2017.1283188. PMC 5305167. PMID 28229088.
- Noctor G, Foyer CH (June 1998). "Ascorbate and Glutathione: Keeping Active Oxygen Under Control". Annual Review of Plant Physiology and Plant Molecular Biology. 49 (1): 249–279. doi:10.1146/annurev.arplant.49.1.249. PMID 15012235.
- Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS (June 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. PMC 144235. PMID 10368185.
- Parisy V, Poinssot B, Owsianowski L, Buchala A, Glazebrook J, Mauch F (January 2007). "Identification of PAD2 as a gamma-glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis" (PDF). The Plant Journal. 49 (1): 159–72. doi:10.1111/j.1365-313X.2006.02938.x. PMID 17144898.
- Rouhier N, Lemaire SD, Jacquot JP (2008). "The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation". Annual Review of Plant Biology. 59 (1): 143–66. doi:10.1146/annurev.arplant.59.032607.092811. PMID 18444899.
- Allen J, Bradley RD (September 2011). "Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers". Journal of Alternative and Complementary Medicine. 17 (9): 827–33. doi:10.1089/acm.2010.0716. PMC 3162377. PMID 21875351.
- Witschi A, Reddy S, Stofer B, Lauterburg BH (1992). "The systemic availability of oral glutathione". European Journal of Clinical Pharmacology. 43 (6): 667–9. doi:10.1007/bf02284971. PMID 1362956.
- "Acetylcysteine Monograph for Professionals - Drugs.com".
- Zhang J, Zhou X, Wu W, Wang J, Xie H, Wu Z (2017). "Regeneration of glutathione by α-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity". Environ Toxicol Pharmacol. 51: 30–37. doi:10.1016/j.etap.2017.02.022. PMID 28262510.
- Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D (April 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.
- van Groningen L, Opdenoordt S, van Sorge A, Telting D, Giesen A, de Boer H (April 2010). "Cholecalciferol loading dose guideline for vitamin D-deficient adults". European Journal of Endocrinology. 162 (4): 805–11. doi:10.1530/EJE-09-0932. PMID 20139241.
- Lieber CS (November 2002). "S-adenosyl-L-methionine: its role in the treatment of liver disorders". The American Journal of Clinical Nutrition. 76 (5): 1183S–7S. doi:10.1093/ajcn/76.5.1183s. PMID 12418503.
- Vendemiale G, Altomare E, Trizio T, Le Grazie C, Di Padova C, Salerno MT, Carrieri V, Albano O (May 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 (September 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. 29 (5): 597–604. doi:10.1093/oxfordjournals.alcalc.a045589. PMID 7811344.
- Dröge W, Holm E (November 1997). "Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction". FASEB Journal. 11 (13): 1077–89. doi:10.1096/fasebj.11.13.9367343. PMID 9367343.
- Tateishi N, Higashi T, Shinya S, Naruse A, Sakamoto Y (January 1974). "Studies on the regulation of glutathione level in rat liver". Journal of Biochemistry. 75 (1): 93–103. doi:10.1093/oxfordjournals.jbchem.a130387. PMID 4151174.
- Meyer AJ, May MJ, Fricker M (July 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.
- Sebastià J, Cristòfol R, Martín M, Rodríguez-Farré E, Sanfeliu C (January 2003). "Evaluation of fluorescent dyes for measuring intracellular glutathione content in primary cultures of human neurons and neuroblastoma SH-SY5Y". Cytometry. Part A. 51 (1): 16–25. doi:10.1002/cyto.a.10003. PMID 12500301.
- Lantz RC, Lemus R, Lange RW, Karol MH (April 2001). "Rapid reduction of intracellular glutathione in human bronchial epithelial cells exposed to occupational levels of toluene diisocyanate". Toxicological Sciences. 60 (2): 348–55. doi:10.1093/toxsci/60.2.348. PMID 11248147.
- Jiang X, Yu Y, Chen J, Zhao M, Chen H, Song X, Matzuk AJ, Carroll SL, Tan X, Sizovs A, Cheng N, Wang MC, Wang J (March 2015). "Quantitative imaging of glutathione in live cells using a reversible reaction-based ratiometric fluorescent probe". ACS Chemical Biology. 10 (3): 864–74. doi:10.1021/cb500986w. PMC 4371605. PMID 25531746.
- Jiang X, Chen J, Bajić A, Zhang C, Song X, Carroll SL, Cai ZL, Tang M, Xue M, Cheng N, Schaaf CP, Li F, MacKenzie KR, Ferreon AC, Xia F, Wang MC, Maletić-Savatić M, Wang J (July 2017). "Quantitative imaging of glutathione". Nature Communications. 8: 16087. doi:10.1038/ncomms16087. PMC 5511354. PMID 28703127.
- Chen J, Jiang X, Zhang C, MacKenzie KR, Stossi F, Palzkill T, Wang MC, Wang J (2017). "Reversible Reaction-Based Fluorescent Probe for Real-Time Imaging of Glutathione Dynamics in Mitochondria". ACS Sensors. 2 (9): 1257–1261. doi:10.1021/acssensors.7b00425. PMC 5771714. PMID 28809477.
- Meyer AJ, Brach T, Marty L, Kreye S, Rouhier N, Jacquot JP, Hell R (December 2007). "Redox-sensitive GFP in Arabidopsis thaliana is 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 G, Labate V, Mele M, Panieri E, Arcovito G, Galeotti T, Østergaard H, Winther JR, De Spirito M, Pani G (October 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.
- Giustarini D, Dalle-Donne I, Milzani A, Fanti P, Rossi R (September 2013). "Analysis of GSH and GSSG after derivatization with N-ethylmaleimide". Nature Protocols. 8 (9): 1660–9. doi:10.1038/nprot.2013.095. PMID 23928499.
- Schwarzländer M, Dick T, Meyer AJ, Morgan B (April 2016). "Dissecting Redox Biology Using Fluorescent Protein Sensors". Antioxidants & Redox Signaling. 24 (13): 680–712. doi:10.1089/ars.2015.6266. PMID 25867539.
- Farkas E, Buglyó P (2017). "Chapter 8. Lead(II) Complexes of Amino Acids, Peptides, and Other Related Ligands of Biological Interest". In Astrid S, Helmut S, Sigel RK (eds.). Lead: Its Effects on Environment and Health. Metal Ions in Life Sciences. 17. de Gruyter. pp. 201–240. doi:10.1515/9783110434330-008. ISBN 9783110434330. PMID 28731301.
- Balendiran GK, Dabur R, Fraser D (2004). "The role of glutathione in cancer". Cell Biochemistry and Function. 22 (6): 343–52. doi:10.1002/cbf.1149. PMID 15386533.
- Visca A, Bishop CT, Hilton SC, Hudson VM (2008). "Improvement in clinical markers in CF patients using a reduced glutathione regimen: An uncontrolled, observational study". Journal of Cystic Fibrosis. 7 (5): 433–6. doi:10.1016/j.jcf.2008.03.006. PMID 18499536.CS1 maint: multiple names: authors list (link)
- Bishop C, Hudson VM, Hilton SC, Wilde C (January 2005). "A pilot study of the effect of inhaled buffered reduced glutathione on the clinical status of patients with cystic fibrosis". Chest. 127 (1): 308–17. doi:10.1378/chest.127.1.308. PMID 15653998.
- Mandal PK, Tripathi M, Sugunan S (January 2012). "Brain oxidative stress: detection and mapping of anti-oxidant marker 'Glutathione' in different brain regions of healthy male/female, MCI and Alzheimer patients using non-invasive magnetic resonance spectroscopy". Biochemical and Biophysical Research Communications. 417 (1): 43–48. doi:10.1016/j.bbrc.2011.11.047. PMID 22120629.
- Mandal PK, Saharan, S, Tripathi M, Murari G (October 2015). "Brain Glutathione Levels – A Novel Biomarker for Mild Cognitive Impairment and Alzheimer's Disease". Biological Psychiatry. 78 (10): 702–710. doi:10.1016/j.biopsych.2015.04.005. PMID 26003861.
- Rigaud J, Cheynier V, Souquet J, Moutounet M (1991). "Influence of must composition on phenolic oxidation kinetics". Journal of the Science of Food and Agriculture. 57 (1): 55–63. doi:10.1002/jsfa.2740570107.
- Vallverdú-Queralt A, Verbaere A, Meudec E, Cheynier V, Sommerer N (January 2015). "Straightforward method to quantify GSH, GSSG, GRP, and hydroxycinnamic acids in wines by UPLC-MRM-MS". Journal of Agricultural and Food Chemistry. 63 (1): 142–9. doi:10.1021/jf504383g. PMID 25457918.
- Malathi, M; Thappa, DM (2013). "Systemic skin whitening/lightening agents: what is the evidence?". Indian Journal of Dermatology, Venereology and Leprology. 79 (6): 842–6. doi:10.4103/0378-6323.120752. PMID 24177629.
- Dilokthornsakul, W; Dhippayom, T; Dilokthornsakul, P (June 2019). "The clinical effect of glutathione on skin color and other related skin conditions: A systematic review". Journal of Cosmetic Dermatology. 18 (3): 728–737. doi:10.1111/jocd.12910. PMID 30895708.
- Sonthalia, Sidharth; Daulatabad, Deepashree; Sarkar, Rashmi (2016). "Glutathione as a skin whitening agent: Facts, myths, evidence and controversies". Indian J. Dermatol. Venereol. Leprol. 82 (3): 262–72. doi:10.4103/0378-6323.179088. PMID 27088927.
- Bilinsky LM, Reed MC, Nijhout HF (July 2015). "The role of skeletal muscle in liver glutathione metabolism during acetaminophen overdose". Journal of Theoretical Biology. 376: 118–33. doi:10.1016/j.jtbi.2015.04.006. PMC 4431659. PMID 25890031. Lay summary – ALN Magazine (24 June 2015).
- Drevet JR (May 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 G, Fang YZ, Yang S, Lupton JR, Turner ND (March 2004). "Glutathione metabolism and its implications for health". The Journal of Nutrition. 134 (3): 489–92. doi:10.1093/jn/134.3.489. PMID 14988435.