Welcome to University of Mumbai, Department of Biophysics

Bioinformatics Database on
"Radiosensitisers and Radioprotectors"

Alphabetical Search   >  G   >  Glutathione                                                                                                                                                                 Top


Go To:

General Features                  Clinical Study                  Chemical Intervention                 Pharmacological Aspects                 
Radiobiological Aspects                  Biological Models                  Biological Target                  Toxicity                 


Name: Glutathione
Generic Names/
L-g-glutamyl-L- cysteinylglycine[1]
Trade Names: RayGelTM (reduced glutathione and anthocyanins; Integrative Therapies, Portland, OR)[4]
IUPAC name: (2S)-2-amino-4-{[(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl]carbamoyl}butanoic acid[5]
2-amino-5-{[2-carboxymethyl)-amino]-1-(mercaptomethyl)-2-oxoethyl]-amino}-5-oxopentanoic acid) [6],[7],[8]
Molecular Weight: 307 g/mol[9]
307.3235 g/mol [7]
Structure: [10],[11],[12],[8]
Functional Group/
It is a tri-peptide composed of non-essential amino acids(g-glutamyl-cysteinyl-glycine)[2],[13]
γ-glutamyl linkage and sulphydryl group (–SH)[1]
sulphydryl group (–SH)[14]
has both amide and amine groups[3]
Chemical Nature: Intracellular thiol antioxidant[13],[15]
Found in cells as reduced (GSH) and oxidized form(GSSG)[1], also as mixed disulfide with protein and non-protein sulfhydryls, thiol esters of GSH[11]
It is water soluble in nature and has melting point of 383°F/195°C. [7]
GSH acts as electron carriers[8]
GSH has a net charge of- 1 at neutral pH[17]
It has approximate net charge of -1 at pH 7[42]
Synthesis: Although synthesized naturally in all tissues[10], synthesized more in liver[18],[10]
Synthesized intracellularly by γ-glutamylcysteine synthetase and GSH synthetase, requiring ATP[2],[11]
Functions: Chief nonprotein intracellular sulfhydryl[11]
Acts as a cofactor for Glutaredoxins[19]
glutathione is a coenzyme for several reactions.[20], it conjugates with foreign compounds, drugs [21]
Glutathione appaers to be a storage form and a transport form of amino acid 'cysteine' [21] Maintains intracellular redox status through reduced glutathione(GSH)/oxidized glutathione(GSSG) system and glutaredoxin system, functions directly or indirectly in many important phenomema including synthesis of protein and DNA, transport, enzyme activity, metabolism and cell protection[22]
Endogenous glutathione takes part in cellular antioxic and defensive function
non-antioxidant functions involve modulation of cell proliferation and immune response
prooxidant reactions induced by GSH catabolsim appeared to modulate cellular signal transduction chains such as cell surface receptors, protein phosphatase activities. [15],[23]
GSH in lens maintains protein thiols in the reduced state, preventing the formation of high molecular weight protein aggregates, protect membrane -SH groups that are important in cation transport and permeability, detoxifies hydrogen peroxide and other organoperoxides in aqueous humor of eye[24]
the GSH oxidation-reduction cycle helps maintain structural and functional viability in spite of endogenous production of reactive oxygen intermediates in many cell types[11]
Glutathione is involved in the disposal of peroxides by brain cells and in the protection against reactive oxygen species.[25]
plays role in metal homeostasis and signal transduction under metal stress[26]
major protective role against the reactive drug intermediates generated by bioreduction is provided by the ubiquitous glutathione redox cycle. glutathione redox cycle has a vital role in the cellular response to bio-reduction and activation of various classes of compounds. The regulatory role of glutathione is very evident in the utilization of reducing equivalents [27]
The metabolic role of glutathione was investigated with emphasis on oxidative transitions associated with hydroperoxide and drug metabolism. Hydroperoxide reduction is catalyzed by the GSH peroxidases (Se dependent or non-Se dependent) and leads to the formation of glutathione disulfide. Intracellularly, a steady state is maintained (a) by the activity of GSSG reductase operating at the expense of NADPH, and (b) by an efflux of GSSG from the cell.[28]
plasma glutathione plays role in the interorgan relationships in glutathione turnover[28]
& Indications:
Pharmcological Action-
Amino thiol radioprotector[29]
Therapeutic indications:
Preclinical study-
Increase in glutathione in brain is suggested to be promising therpy for Alzheimer's disease[2]
The prior administration of glutathione (GSH) partially prevented carbon tetrachloride (CCl4)-induced liver necrosis in rats in vivo[31]
early and delayed treatment with GSH prevented peroxynitrite-mediated acetaminophen hepatotoxicity in mice[32]
Exogenous GSH protected rat small-intestinal epithelial cells against oxidative chemical injury induced by t-butyl hydroperoxide[33]
exogenous GSH is could be a promising for the treatment of anemia in most hemodialyzed patients[34]
It has been suggested to be a candidate as an adjunctive in management of periodontitis[7]
Monoethyl (MEE) and diethyl (DEE) esters of glutathione (GSH) exhibited some protection of normal and buthionine sulfoximine (BSO) pretreated cells against X-irradiation[35]
y-glutamylcysteinylglycyl monomethyl (or monoethyl) ester is speculated to offer protection against radiation[36]
Administration of the glutathione monoester prevented the marked decline of mitochondrial glutathione produced by buthionine sulfoximine in skeletal muscle and increased the level of glutathione in heart mitochondria of mice[37]
monoethyl ester of glutathione was found to protect human lymphoid cells of the CEM line against the lethal effects of irradiation, when given prior to radiation[38].
Notes: Blood glutathione(glutathione redox ratio in blood) can be used as an index of radiation-induced oxidative stress, as reported in a study with mice and human[39]
glutathione diethyl ester is highly effective as a delivery agent for glutathione monoester, and thus for glutathione, in human cells, hence suggested to have significant practical application[40]
dominant apoptosis resistance is found to be dependent, at least in part, on intracellular GSH levels in leukemia cells[41]
oxidised glutathione , glutathione sulphinic acid γ-glutamylalanylglycine , γ-glutamylserylglycine, and hydrogen peroxide have been found to form in the 60Co γ radiolysis of aerated reduced glutathione solutions at pH values between 1-7.3[14]
concentration of GSH during the treatment of locally advanced cervical cancer is suggested be important for the prediction of the efficacy of the treatment(neoadjuvant chemotherapy followed by concurrent chemoradiation) in a clinical study[43]
1. Abdalla MY, Glutathione as potential target for cancer therapy; more or less is good? (Mini-review). Jordan Journal of Biological Sciences. 2011;4(3):119-124.
2. Butterfield DA, Pocernich CB, Drake J, Elevated glutathione as a therapeutic strategy in Alzheimer's disease. Drug Development Research. 2002;56(3):428-437.
3. Sjöberg L, Eriksen TE, Révész L, The reaction of the hydroxyl radical with glutathione in neutral and alkaline aqueous solution. Radiat Res. 1982 ;89(2):255-63.
4. Miko ET et al, Combination glutathione and anthocyanins as an alternative for skin care during external-beam radiation. Am J Surg. 2005;189(5):627-30; discussion 630-1.
5. Chapter 22: Determination of glutathione by Shpigun LK,Section IV: Natural Antioxidants ;In: Flow injection analysis of food additives by Ruiz-Capillas C, Nollet L, CRS Press, Taylor Francis Group, Florida, page no. 425.
6. Dictionary of Flavors, second edition by Dolfe De Rovira, Sr, Wiley-Blackwell publications, 2008, page no. 21.
7. Bains VK, Bains R, The antioxidant master glutathione and periodontal health. Dent Res J (Isfahan). 2015 ;12(5):389-405.
8. Dhivya H, Glutathione ─ a master antioxidant and an immune system modulator. Journal of Biological and Information Sciences. 2012;1(3):28-30.
9. Kendall EC, Mckenzie BF, Mason HL, A study of glutathione. I. Its preparation in crystalline form and its identification. The Journal of Biological Chemistry. 1929; 84:657-674.
10. Hospers GA, Eisenhauer EA, de Vries EG, The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects. Br J Cancer. 1999;80(5-6):629-38.
11. Arrick BA, Nathan CF, Glutathione metabolism as a determinant of therapeutic efficacy: a review. Cancer Res. 1984;44(10):4224-32.
12. Hanigan MH, Pitot HC, Gamma-glutamyl transpeptidase--its role in hepatocarcinogenesis. Carcinogenesis. 1985;6(2):165-72.
13. Machlin LJ, Bendich A, Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1987;1(6):441-5.
14. Lal M,60Co γ radiolysis of reduced glutathione in aerated solutions at pH values between 1–7.0. Can. J. Chem. 1976, 54(7): 1092-1097.
15. Paolicchi A et al, Glutathione catabolism as a signaling mechanism. Biochem Pharmacol. 2002;64(5-6):1027-35.
16. Mans DR et al, Reactions of glutathione with the catechol, the ortho-quinone and the semi-quinone free radical of etoposide. Consequences for DNA inactivation. Biochem Pharmacol. 1992;43(8):1761-8.
17. Smoluk GD, Fahey RC, Ward JF, Interaction of glutathione and other low-molecular-weight thiols with DNA: evidence for counterion condensation and coion depletion near DNA. Radiat Res. 1988;114(1):3-10.
18. Chapter 107: Detoxificaton by Salguero ML; In: Integrative Medicine, second edition, by Rakel D, Saunders, Elsevier, Philadelphoa 2007, page no. 1130.
19. Chatterjee A, Reduced Glutathione: A Radioprotector or a Modulator of DNA-Repair Activity? Nutrients 2013; 5(2): 525-542.
20. Meister A, Selective modification of glutathione metabolism. Science. 1983;220(4596):472-7.
21. Meister A, Anderson ME, Glutathione. Annu Rev Biochem. 1983;52:711-60.
22. Chapter 3: Radioenhancement by targeting cellular redox pathways and/or by incorporation of High-Z material in to target:section 3.4 Radiosensitization by targeting the GSH/GSSG system; In : Radiosensitizers and Radiochemotherapy in the Treatment of Cancer by Lehnert S, CRC Press, Taylor and Fancis group, Florida, page no. 88.
23. Dröge W, Free radicals in the physiological control of cell function. Physiol Rev. 2002;82(1):47-95.
24. Reddy VN, Glutathione and its function in the lens - an overview. Exp Eye Res. 1990;50(6):771-8.
25. Dringen R, Metabolism and functions of glutathione in brain. Prog Neurobiol. 2000;62(6):649-71.
26. Jozefczak M et al, Glutathione is a key player in metal-induced oxidative stress defenses. Int J Mol Sci. 2012; 13(3): 3145–3175.
27. Reed DJ, Regulation of reductive processes by glutathione. Biochem Pharmacol. 1986;35(1):7-13.
28. Sies H et al, Functions of intracellular glutathione in hepatic hydroperoxide and drug metabolism and the role of extracellular glutathione. Adv Enzyme Regul. 1980;18:303-20.
29. Nair CK, Parida DK, Nomura T, Radioprotectors in radiotherapy. J Radiat Res. 2001;42(1):21-37.
30. Hong SY et al, Effects of N-acetyl-L-cysteine and glutathione on antioxidant status of human serum and 3T3 fibroblasts. J Korean Med Sci 2003; 18(5): 649-54.
31. Gorla N et al, Studies on the mechanism of glutathione prevention of carbon tetrachloride-induced liver injury. Br J Exp Pathol. 1983; 64(4): 388–395.
32. Knight TR et al, Peroxynitrite is a critical mediator of acetaminophen hepatotoxicity in murine livers: protection by glutathione. J Pharmacol Exp Ther. 2002 ;303(2):468-75.
33. Lash LH, Hagen TM, Jones DP, Exogenous glutathione protects intestinal epithelial cells from oxidative injury. Proc Natl Acad Sci U S A. 1986; 83(13): 4641–4645.
34. Usberti M et al, Effect of exogenous reduced glutathione on the survival of red blood cells in hemodialyzed patients. J Nephrol. 1997;10(5):261-5.
35. Vos O, Roos-Verhey WS, Radioprotection by glutathione esters and cysteamine in normal and glutathione-depleted mammalian cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1988 ;53(2):273-81.
36. Puri RN, Meister A, Transport of glutathione, as gamma-glutamylcysteinylglycyl ester, into liver and kidney. Proc Natl Acad Sci U S A. 1983 ;80(17):5258-60.
37. Mårtensson J, Meister A, Mitochondrial damage in muscle occurs after marked depletion of glutathione and is prevented by giving glutathione monoester. Proc Natl Acad Sci U S A. 1989;86(2):471-5.
38. Wellner VP et al, Radioprotection by glutathione ester: transport of glutathione ester into human lymphoid cells and fibroblasts. Proc Natl Acad Sci U S A. 1984 ;81(15):4732-5.
39. Navarro J et al, Blood glutathione as an index of radiation-induced oxidative stress in mice and humans. Free Radic Biol Med. 1997;22(7):1203-9.
40. Levy EJ, Anderson ME, Meister A, Transport of glutathione diethyl ester into human cells. Proc Natl Acad Sci U S A. 1993; 90(19): 9171–9175.
41. Friesen C, Kiess Y, Debatin KM, A critical role of glutathione in determining apoptosis sensitivity and resistance in leukemia cells. Cell Death Differ. 2004;11 Suppl 1:S73-85.
42. Zheng S et al, Radioprotection of DNA by thiols: relationship between the net charge on a thiol and its ability to protect DNA. Radiat Res. 1988;114(1):11-27.
43. Daukantienė L et al, The significance of reduced glutathione and glutathione S-transferase during chemoradiotherapy of locally advanced cervical cancer. Medicina. 2014;50(4):222–229.