GSH is a primary protectant of skin, lens, cornea, and retina against radiation damage and other biochemical foundations of P detoxification in the liver, kidneys, lungs, intestinal, epithelia and other organs. GSH is the essential cofactor for many enzymes that require thiol-reducing equivalents, and helps keep redox-sensitive active sites on enzyme in the necessary reduced state.
GSH and its metabolites also interface with energetics and neurotransmitter syntheses through several prominent metabolic pathways. GSH availability down-regulates the pro-inflammatory potential of leukotrienes and other eicosanoids.
Monograph provided by Alternative Medicine Review thorne. Birmingham, AL What is Glutathione? Mechanism of Action GSH is an extremely important cell protectant. This product is not meant to diagnose, treat, cure, or prevent any disease.
Nutrition 18 : — Lei , X. FEBS Lett. Guarino , M. News Physiol. Cai , J. Sen , C. Turrens , J. Oxford University Press is a department of the University of Oxford.
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Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. GSH Synthesis. Interorgan GSH Transport. Roles of GSH. Concluding Remarks and Perspectives. Glutathione Metabolism and Its Implications for Health. Guoyao Wu , Guoyao Wu. E-mail: g-wu tamu. Oxford Academic. Yun-Zhong Fang. Sheng Yang. Joanne R. Nancy D. Revision received:. Select Format Select format.
Permissions Icon Permissions. Open in new tab Download slide. Open in new tab. Google Scholar Crossref. Search ADS. Cysteine supplementation improves the erythrocyte glutathione synthesis rate in children with severe edematous malnutrition.
In vivo rates of erythrocyte glutathione synthesis in children with severe protein-energy malnutrition. Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet.
Plasma Loxoproline kinetics and whole blood glutathione synthesis rates in severely burned adult humans. Cysteine metabolism in periportal and perivenous hepatocytes: perivenous cells have greater capacity for glutathione production and taurine synthesis but not for cysteine catabolism.
It is made of three types of molecules known as amino acids. One unique thing about glutathione is that the body is able to make it in the liver, which is not true of most antioxidants.
Researchers have found links between low levels of glutathione and some diseases. It is possible to increase glutathione levels through oral or intravenous IV supplementation. Another option is to take supplements that activate the natural glutathione production in the body. These supplements include:. Reducing toxin exposure and increasing intake of healthful foods are also excellent ways to naturally increase glutathione levels.
Free radicals may contribute to aging and some diseases. Antioxidants help to counteract free radicals and protect the body from their damaging effects. Glutathione is a very strong antioxidant, partly because high concentrations can be found in every cell in the body.
Some research shows that glutathione has a role in preventing the progression of cancer. However, the same research indicates that glutathione may make tumors less sensitive to chemotherapy , which is a common cancer treatment. Hepatitis , alcohol abuse, and fatty liver disease all damage the cells of the liver. A small clinical trial concludes that glutathione could help treat nonalcoholic fatty liver disease due to its antioxidant properties and potential to detoxify.
New approaches, particularly to resolve in vivo glutathione quantification, are needed to solve these and related problems. Therefore, a scheme for investigation of potential chemicals, pharmaceuticals, or phytochemicals that target GSH homeostasis may be proposed.
At the first stage of investigation, cell cultures and unicellular organisms can be used to identify potential candidate compounds and potential effectors and, if possible, to identify mechanisms involved. Selected compounds would then be evaluated at the whole organism level. Studies with D. Zebrafish Danio rerio also can be used as an alternative genetically tractable model organism, the genome of which has been sequenced, and many tools for molecular interventions in this organism have been developed.
If successful in these organisms, candidate compounds of interest may then be studied in mammalian models. The development of molecular biological tools and production of lines with deleted genes or chimeric lines may also provide some additional information. Research with genetically transformed mice would provide the most useful information, but they are expensive and time consuming to work with.
So, the final strategy would depend on many circumstances and rely on the facilities available, particular interests, skills and experience of reserchers.
The author is grateful to Dr. Arthur J. Cooper for critical analysis of the paper and a number of suggestions and ideas, Janet M. Storey, Halyna M. Semchyshyn, Maria M. Bayliak, and Olha I. Kubrak for the critical reading of the paper and Nadia M. Semchuk, Halyna V. Shmigel, and Ludmyla M.
Lozinsla for the excellent technical assistance during paper preparation. The author is grateful also to two anonymous referees for highly professional, critical, detailed and constructive analysis of the paper and a number of suggestions, ideas, and propositions which helped to improve the paper.
The work of the author was partially supported by a grant from the Ministry of Education and Science of Ukraine U This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Special Issues. Academic Editor: Arthur J. Received 28 Jan Revised 30 Aug Accepted 24 Oct Published 28 Feb Abstract Glutathione GSH is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. Introduction Glutathione GSH is a tripeptide L- -glutamyl-L-cysteinyl-glycine with multiple functions in living organisms [ 1 — 4 ].
Figure 1. Glutathione is a tripeptide: L- -glutamyl-L-cysteinyl-glycine. In its reduced form a the N-terminal glutamate and cysteine are linked by the -carboxyl group of glutamate, preventing cleavage by common cellular peptidases and restricting cleavage to -glutamyltranspeptidase. The cysteine residue is the key functional component of glutathione, providing a reactive thiol group that plays an essential role in its functions.
Furthermore, cysteine residues form the intermolecular dipeptide bond in the oxidized glutathione molecule b. Figure 2. Glutathione homeostasis involves both intra- and extracellular mechanisms.
Glutathione is synthesized in both de novo and salvage synthesis pathways. De novo synthesis requires the three amino acids and energy in the form of ATP. Glutamate may be provided in part from the conversion of a -glutamyl amino acid to 5-oxoproline, which is then converted to glutamate.
Salvage synthesis involves either reduction of GSSG or uses precursors formed from the hydrolysis of GSH or its conjugates by -L-glutamyl transpeptidase at the external surface of the plasma membrane that are transported back into the cell as amino acids or dipeptides. GSH is consumed in various processes. In addition to detoxification of reactive species and electrophiles such as methylglyoxal, GSH is involved in protein glutathionylation and several other processes, such as the biosynthesis of leukotrienes and prostaglandins, and reduction of ribonucleotides.
Modified from [ 27 ]. Figure 3. Involvement of glutathione in elimination of reactive oxygen and nitrogen species. Hydrogen peroxide may be removed by catalase or by glutathione peroxidase GPx. The latter requires GSH to reduce peroxide. Figure 4. The dynamics of reactive oxygen species in biological systems. Steady-state levels of reactive oxygen species fluctuate over a certain range under normal conditions.
However, under stress ROS levels may increase or decrease beyond the normal range resulting in acute or chronic oxidative or reductive stress. Under some conditions, ROS levels may not return to their initial range and stabilize at a new quasistationary level. Figure 5.
Under nonstressed conditions the transcription factor Nrf2 binds to the Keap1 homodimer. The resulting protein complex can then further complex with Cullin 3 leading to ubiquitination of Nrf2 followed by proteasomal degradation.
Nrf2 migration into the nucleus is promoted by at least three different mechanisms: oxidation of Keap thiol groups to form disulfides, modification of Keap1 cysteine residues by electrophiles, or phosphorylation of Nrf2 by protein kinases that, in turn, may be activated by oxidants.
Figure 6. Oxidation of protein cysteine residues to sulfenic, sulfinic, or sulfonic derivatives and formation of glutathionylated proteins. In biological systems, sulfenic and sulfinic derivatives may be reduced by thioredoxin TR and sulfiredoxin Srx , respectively, whereas sulfonic moieties cannot be reduced. Glutathionylated proteins are formed by direct interaction of GSH with sulfenic acid derivatives, exchange between cysteine residues and GSSG, or interaction with oxidized glutathione forms.
Table 1. Figure 7. Involvement of glutathione in the detoxification of xenobiotics and reactive oxygen species, its relationship with pathological development and the potential role of different phytochemicals.
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