Glutathione chemical structure

Glutathione

An intracellular thiol-based antioxidant found in nearly all biological cells, considered the most abundant endogenous antioxidant in humans [3, 9]. The tripeptide Glutathione (GSH), is composed of three amino acids; glycine, glutamate, and cysteine. However GSH synthesis is foremost reliant on cysteine (availability of cysteine makes GSH synthesis possible and γ-glutamate-cysteine ligase is the rate-limiting enzyme). The first step requires cysteine and the entire compound is dependent on the thiol group of the cysteine molecule [3, 9, 11]. Thiols are organosulfur compounds, they contain a sulfhydryl group (SH).

 

GSH as an antioxidant, scavenges free radicals, chelates heavy metals, detoxifies xenobiotics, and reduces general oxidative stress. GSH is deemed “the mother of all antioxidants.” Endogenously produced, researchers have reported age-related decline in bodily GSH levels and a compromised metabolic pathways due to certain disease states/conditions [5, 6, 7, 8, 10]. Low to deficient GSH levels have been shown to contribute to anemia, seizures, and neurodegeneration [2].

 

GSH protects mitochondrial function and integrity. Fighting oxidative stress caused by free radical byproducts of cellular respiration in the mitochondria, environmental stressors/exogenous chemicals, and general toxins in the body. Studies have concluded that a new method to approaching longevity and healthy aging is improving GSH levels and preventing deficiencies. GSH also crosses the blood brain barrier and is the main source of cysteine in the brain, an amino acid that is then the main thiol source in the brain [1].

 

Supplementation to increase cysteine amounts bolsters GSH synthesis and prevents deficiencies [5]. GSH in turn supports and detoxifies a multitude of biological reactions.

 

Sources

1. Aoyama, K., & Nakaki, T. (2013). Impaired glutathione synthesis in neurodegeneration. International journal of molecular sciences, 14(10), 21021–21044. doi:10.3390/ijms141021021
2. Ballatori, N. (2008). Glutathione dysregulation and the etiology and progression of human diseases. Biological Chemistry, 390(3), 191-214.
3. Espinosa-Diez, C., Miguel, V., Mennerich, D., Kietzmann, T., Sánchez-Pérez, P., Cadenas, S., & Lamas, S. (2015). Antioxidant responses and cellular adjustments to oxidative stress. Redox biology, 6, 183-197.
4. Forman, H. J., Zhang, H., & Rinna, A. (2008). Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular aspects of medicine, 30(1-2), 1-12.
5. Guoyao Wu, Yun-Zhong Fang, Sheng Yang, Joanne R. Lupton, Nancy D. Turner, Glutathione Metabolism and Its Implications for Health, The Journal of Nutrition, Volume 134, Issue 3, March 2004, Pages 489–492.
6. J. Lyons, A. Rauh-Pfeiffer, Y. M. Yu, X.-M. Lu, D. Zurakowski, R. G. Tompkins, . . . L. Castillo. (2000). Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet. Proceedings of the National Academy of Sciences of the United States of America, 97(10), 5071-5076.
7. McCarty, M. F., & DiNicolantonio, J. J. (2015). An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly. Age (Dordrecht, Netherlands), 37(5), 96. doi:10.1007/s11357-015-9823-8
8. Minette Lagman, Judy Ly, Tommy Saing, Manpreet Kaur Singh, Enrique Vera Tudela, Devin Morris, . . . Vishwanath Venketaraman. (2015). Investigating the causes for decreased levels of glutathione in individuals with type II diabetes. PLoS ONE, 10(3), E0118436.
9. Pizzorno J. (2014). Glutathione!. Integrative medicine (Encinitas, Calif.), 13(1), 8-12.
10. R Sekhar, P Kumar, C Liu, REVERSING AGING: PREVENTING AGE-RELATED DECLINE IN GLUTATHIONE AND MITOCHONDRIAL FUNCTION INCREASES LONGEVITY, Innovation in Aging, Volume 2, Issue suppl_1, November 2018, Page 887.
11. Yu, X., & Long, Y. (n.d.). Crosstalk between cysteine and glutathione is critical for the regulation of amino acid signaling pathways and ferroptosis. Sci Rep, 6(1), 30033.

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