Gamma-glutamylcysteine (GGC) is a dipeptide and is the immediate precursor to the tripeptide glutathione (GSH). The intracellular concentration of gamma-glutamylcysteine (GGC) is generally low because gamma-glutamylcysteine (GGC) reacts rapidly with glycine to form glutathione (GSH). This second and final reaction step in glutathione biosynthesis is catalyzed by the activity of the ATP dependent glutathione synthase (GS) enzyme.
Gamma-glutamylcysteine (GGC) is essential to mammalian life. Mice that have had the glutamate-cysteine ligase (GCL) gene knocked out do not develop beyond the embryo stage and die before birth [5]. This is because gamma-glutamylcysteine (GGC) is vital for the biosynthesis of glutathione (GSH). Since the production of cellular gamma-glutamylcysteine (GGC) in humans slows down with age, as well as during the progression of many chronic diseases, it has been postulated that supplementation with gamma-glutamylcysteine (GGC) could offer health benefits. Other benefits of gamma-glutamylcysteine (GGC) supplementation may extend to situations where glutathione (GSH) has been acutely lowered below optimum such as following strenuous exercise, and during trauma or episodes of poisoning.
Several review articles have been published regarding the therapeutic potential of gamma-glutamylcysteine (GGC) to replenish glutathione in age-related [6] and chronic disease states such as Alzheimer’s disease [7]. Gamma-glutamylcysteine (GGC) is also capable of being a powerful antioxidant in its own right [8-10].
A human clinical study in healthy, non-fasting adults demonstrated that orally administered gamma-glutamylcysteine (GGC) can significantly increase lymphocyte glutathione (GSH) levels indicating systemic bioavailability, validating the therapeutic potential of gamma-glutamylcysteine (GGC) [16].
Animal model studies with gamma-glutamylcysteine (GGC) have supported it’s potential therapeutic role in both the reduction of oxidant stress-induced damage in tissues including the brain [17] and as a treatment for sepsis [18].
Supplementation with glutathione (GSH) is incapable of increasing cellular glutathione (GSH) since the glutathione (GSH) concentration found in the extracellular environment is much lower than that found intracellularly by about a thousand-fold. This large difference means that there is an insurmountable concentration gradient that prohibits extracellular glutathione entering cells. Although currently unproven, gamma-glutamylcysteine (GGC) may be the pathway intermediate of glutathione transportation in multicellular organisms [19, 20].
References
- Orlowski, M. and A. Meister, The gamma-glutamyl cycle: a possible transport system for amino acids. Proc Natl Acad Sci U S A, 1970. 67(3): p. 1248-55.
- Meister, A. and M.E. Anderson, Glutathione. Annu Rev Biochem, 1983. 52: p. 711-60.
- Anderson, M.E. and A. Meister, Transport and direct utilization of gamma-glutamylcyst(e)ine for glutathione synthesis. Proceedings of the National Academy of Sciences of the United States of America., 1983. 80(3): p. 707-11.
- Mårtensson, J., Method for determination of free and total glutathione and γ-glutamylcysteine concentrations in human leukocytes and plasma. Journal of Chromatography B: Biomedical Sciences and Applications, 1987. 420(0): p. 152-157.
- Dalton, T.P., et al., Genetically altered mice to evaluate glutathione homeostasis in health and disease. Free Radical Biology and Medicine, 2004. 37(10): p. 1511-1526.
- Ferguson, G. and W. Bridge, Glutamate cysteine ligase and the age-related decline in cellular glutathione: The therapeutic potential of γ-glutamylcysteine. Archives of Biochemistry and Biophysics, 2016. 593: p. 12-23.
- Cao, P., et al., Therapeutic approaches to modulating glutathione levels as a pharmacological strategy in Alzheimer’s disease. Curr Alzheimer Res, 2015. 12(4): p. 298-313.
- Quintana-Cabrera, R. and J.P. Bolanos, Glutathione and gamma-glutamylcysteine in the antioxidant and survival functions of mitochondria. Biochemical Society Transactions, 2013. 41: p. 106-110.
- Quintana-Cabrera, R., et al., γ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor. Nat Commun, 2012. 3: p. 718.
- Nakamura, Y.K., M.A. Dubick, and S.T. Omaye, γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells. Life Sciences, 2011(0).
- Zarka, M.H. and W.J. Bridge, Oral administration of γ-glutamylcysteine increases intracellular glutathione levels above homeostasis in a randomised human trial pilot study. Redox Biology, 2017. 11: p. 631-636.
- Le, T.M., et al., gamma-Glutamylcysteine ameliorates oxidative injury in neurons and astrocytes in vitro and increases brain glutathione in vivo. Neurotoxicology, 2011. 32(5): p. 518-25.
- Yang, Y., et al., γ-glutamylcysteine exhibits anti-inflammatory effects by increasing cellular glutathione level. Redox Biology, 2019. 20: p. 157-166.
- Wu, G., et al., Glutathione metabolism and its implications for health. Journal of Nutrition, 2004. 134(3): p. 489-92.
- Stark, A.A., et al., The role of gamma-glutamyl transpeptidase in the biosynthesis of glutathione. Biofactors, 2003. 17(1-4): p. 139-49.
- Chandler, S.D., et al., Safety assessment of gamma-glutamylcysteine sodium salt. Regulatory Toxicology and Pharmacology, 2012. 64(1): p. 17-25.
- Braidy, N., et al., The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GGC), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by Aβ40 Oligomers in Human Astrocytes. Frontiers in Aging Neuroscience, 2019. 11(177).
- Yang, Y., et al., γ-glutamylcysteine exhibits anti-inflammatory effects by increasing cellular glutathione level. Redox Biology, 2019. 20: p. 157-166.
- Wu, G., et al., Glutathione metabolism and its implications for health. Journal of Nutrition, 2004. 134(3): p. 489-92.
- Stark, A.A., et al., The role of gamma-glutamyl transpeptidase in the biosynthesis of glutathione. Biofactors, 2003. 17(1-4): p. 139-49.
- Chandler, S.D., et al.,Safety assessment of Gamma-glutamylcysteine sodium salt. Regulatory Toxicology and Pharmacology, 2012. 64(1): p. 17-25.
- Braidy, N., et al., The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GAMMA-GLUTAMYLCYSTEINE), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by Aβ40 Oligomers in Human Astrocytes. Frontiers in Aging Neuroscience, 2019. 11(177).
Hi I have Googled for this as stated in your comments and can’t find any products at all. Can you please tell me how to raise this either with supplements or naturally with foods.
Dear Nat, Thanks for your comment. Some of readers have been able to google on Gamma Glutamyl cysteine / GGC supplements successfully. You may try a search on these key words.
Have there been any experiments to show glutathione increases lifespan?
Until recently it has been almost impossible to rapidly and reliably increase cellular glutathione with a drug or supplement. However, with the advent of gamma-glutamylcysteine and its ability to increase cellular glutathione we are hoping that researchers may be able to perform experiments perhaps on animal models to see if it can increase life span. What we can tell you is that there are many observational studies that show a strong correlation with three things:-
1. Cellular glutathione decreases as we get older [1, 2]
2. People suffering chronic diseases have lower cellular glutathione [3, 4]
3. Older populations of people that are relatively healthy and free of disease have higher cellular glutathione than their age matched peers [5]
1. Lenton, K.J., H. Therriault, A.M. Cantin, T. Fülöp, H. Payette, and J.R. Wagner, Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes. The American Journal of Clinical Nutrition, 2000. 71(5): p. 1194-1200. http://www.ajcn.org/content/71/5/1194.abstract
2. van Lieshout, E. and W. Peters, Age and gender dependent levels of glutathione and glutathione S- transferases in human lymphocytes. Carcinogenesis, 1998. 19(10): p. 1873-1875. http://carcin.oupjournals.org/cgi/content/abstract/19/10/1873
3. Lang, C.A., B.J. Mills, W. Mastropaolo, and M.C. Liu, Blood glutathione decreases in chronic diseases. Journal of Laboratory & Clinical Medicine, 2000. 135(5): p. 402-5. http://www.ncbi.nlm.nih.gov/pubmed/10811055
4. Pérez, L.M., B. Hooshmand, F. Mangialasche, P. Mecocci, A.D. Smith, H. Refsum, M. Inzitari, L. Fratiglioni, D. Rizzuto, and A. Calderón-Larrañaga, Glutathione Serum Levels and Rate of Multimorbidity Development in Older Adults. The Journals of Gerontology: Series A, 2019 https://watermark.silverchair.com/glz101.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_
5. Lang, C.A., B.J. Mills, H.L. Lang, M.C. Liu, W.M. Usui, J. Richie, Jr., W. Mastropaolo, and S.A. Murrell, High blood glutathione levels accompany excellent physical and mental health in women ages 60 to 103 years.[comment]. Journal of Laboratory & Clinical Medicine, 2002. 140(6): p. 413-7. https://pubmed.ncbi.nlm.nih.gov/12486409/
I too am looking to obtain Gamma Glutamylcysteine but I can’t find it as a standalone product nor in compound. Do you have any specific products in mind?
We understand that Gamma Glutamylcysteine (GGC) has been incorporated in dietary supplements.
A google search should be able to provide you with information you seek.
Where can I purchase this supplement? GGC?
We understand that Gamma Glutamylcysteine (GGC) has been incorporated in dietary supplements.
A google search should be able to provide you with information you seek.