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Glutathione (GSH)
Master Antioxidant and Cellular Detoxifier

Mammalian cells have evolved numerous mechanisms to prevent or treat injurious events that can result from normal oxidative by-products of cellular metabolism (oxiradicals). Glutathione (GSH) is a tripeptide, found in human cell tissue, formed from the amino acids cysteine, glycine, and glutamic acid.

The "glutathione antioxidant system" is foremost among these internal protective systems because glutathione participates directly in the destruction of reactive oxygen compounds. Glutathione destroys free radicals, is involved in the detoxification of foreign compounds such as carcinogens, etc., and supports the normal active functioning of the immune system. It is our body's Master Antioxidant.

As an antioxidant, glutathione is essential for allowing white blood cells (or lymphocytes) to express their full potential, without being hampered by oxyradical accumulation during the oxygen requiring development of the immune response.

As glutathione levels drop, the person gets sicker. This is because white blood cells and the liver use GSH to detoxify poisons inside the body. When the level decreases, less toxins are able to be eliminated leading to a build up in the body. This leads to increased white blood cell death (due to the cell poisoning itself) and liver impairment.

Glutathione helps detoxify the nicotine and free-radicals in cigarette smokeGlutathione is also required to detoxify the nicotine and free-radicals contained in cigarette smoke - even second hand smoke. It is effective against the toxins contained in the exhaust fumes of motor vehicles and also against pesticides and other environmental toxins.

Glutathione plays a key role in the body’s defense against pollutants and ultraviolet radiation. Removal of heavy metals (mercury, lead, cadmium) from the body requires glutathione. When these toxins combine with glutathione, they form a water soluble compound that can be excreted once and for all by the kidneys.

The highest concentration of glutathione is found in the liver which is the principal organ involved in the detoxification and elimination of toxic materials. Interestingly, glutathione also acts to reconstitute vitamins C and E after they have been oxidized, and therefore plays a determinant role in their function.

Glutathione plays an important role in cancer prevention and treatment. GSH loss or low glutathione levels are implicated in immune compromised individuals, neuro-degenerative diseases such as Multiple Sclerosis, ALS, Alzheimers, and Parkinsons disease, atherosclerosis, hydroxylradical formation, cataracts, damage from many pharmaceutical drugs, cancer and poor survival rates for victims of AIDS.


The Glutathione Antioxidant system

The "glutathione antioxidant system" is among your body's most important internal protective systems because glutathione participates directly in the destruction of reactive oxygen compounds (free radicals or oxiradicals) - the normal oxidative by-products of cellular metabolism.

Glutathione destroys free radicals, is involved in the detoxification of foreign compounds such as carcinogens, etc., and supports the normal active functioning of the immune system.

In the Glutathione Oxidation Reduction (Redox) Cycle, one molecule of (harmful) hydrogen peroxide is reduced to 2 molecules of (harmless) water, while 2 molecules of (reduced) glutathione (GSH) are oxidized in a reaction catalyzed by the enzyme, glutathione peroxidase, which requires selenium as a catalyst.

Hence, GSH is transformed to GSSG. The ratio of GSSG/GSH in the cell is an important marker of oxidative stress. Glutathione reduces toxic substances before they can damage other molecules or important parts of the cell.

Glutathione Disulfide (GSSG) molecule, reduced glutathione

When these toxins combine with glutathione, they form a water soluble compound that can be excreted once and for all by the kidneys. The highest concentration of glutathione is found in the liver which is the principal organ involved in the detoxification and elimination of toxic materials.


See also:

Glutathione: Systemic Protectant Against Oxidative and Free Radical Damage
Parris M. Kidd, Ph.D.

Glutathione metabolism and its implications for health
Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. [J Nutr. 2004 Mar;134(3):489-92.]
Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most abundant low-molecular-weight thiol, and GSH/glutathione disulfide is the major redox couple in animal cells. The synthesis of GSH from glutamate, cysteine, and glycine is catalyzed sequentially by two cytosolic enzymes, gamma-glutamylcysteine synthetase and GSH synthetase. Compelling evidence shows that GSH synthesis is regulated primarily by gamma-glutamylcysteine synthetase activity, cysteine availability, and GSH feedback inhibition. Animal and human studies demonstrate that adequate protein nutrition is crucial for the maintenance of GSH homeostasis. In addition, enteral or parenteral cystine, methionine, N-acetyl-cysteine, and L-2-oxothiazolidine-4-carboxylate are effective precursors of cysteine for tissue GSH synthesis. Glutathione plays important roles in antioxidant defense, nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell proliferation and apoptosis, signal transduction, cytokine production and immune response, and protein glutathionylation). Glutathione deficiency contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases (including kwashiorkor, seizure, Alzheimer's disease, Parkinson's disease, liver disease, cystic fibrosis, sickle cell anemia, HIV, AIDS, cancer, heart attack, stroke, and diabetes). New knowledge of the nutritional regulation of GSH metabolism is critical for the development of effective strategies to improve health and to treat these diseases.

 

 


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