Glutathione

Glutathione is a sulfur-containing amino acid that is an important part of the body's antioxidant defense system. Glutathione is composed of three different amino acids: cysteine, glutamic acid, and glycine. Vitamins B6 and riboflavin are critical for maintaining adequate levels of glutathione within the body.

The term glutathione is typically used as a collective term to refer to the tripeptide L-gamma-glutamyl-L-cysteinylglycine in both its reduced and dimeric forms. Monomeric glutathione is also known as reduced glutathione and its dimer is also known as oxidized glutathione, glutathione disulfide and diglutathione. In this monograph, reduced glutathione will be called glutathione— this is its common usage by biochemists—and the glutathione dimer will be referred to as glutathione disulfide.

Glutathione is widely found in all forms of life and plays an essential role in the health of organisms, particularly aerobic organisms. In animals, including humans, and in plants, glutathione is the predominant non-protein thiol and functions as a redox buffer, keeping with its own SH groups those of proteins in a reduced condition, among other antioxidant activities.

Glutathione is involved in detoxification—it binds to toxins, such as heavy metals, solvents, and pesticides, and transforms them into a form that can be excreted in urine or bile. Glutathione is also an important antioxidant. In preliminary research, dietary glutathione intake from fruit and raw vegetables has been associated with protection against some forms of cancer.1 2 Glutathione has also inhibited cancer in test tube and animal studies. In preliminary research, higher glutathione levels have also been associated with good health in older adults.

Glutathione supplements appear to be efficiently absorbed in rats. However, the same may not be true for glutathione supplements in humans. For example, when seven healthy people were given a single application of up to 3,000 mg of glutathione, there was no increase in blood glutathione levels. The authors of the study concluded "it is not feasible to increase circulating glutathione to a clinically beneficial extent by the oral administrating of a single application of 3,000 mg of glutathione." Absorption of glutathione may be better in rats because unlike the gastrointestinal tract of rats, the human gastrointestinal tract contains significant amounts of an enzyme (gamma-glutamyltranspeptidase) that breaks down glutathione. Preliminary evidence has suggested that absorption of glutathione can occur in the mouth when glutathione tablets are placed between the teeth and the inner cheek.

Glutathione is present in tissues in concentrations as high as one millimolar. Cysteine, the business residue of glutathione, neither has the solubility nor activity of glutathione at physiological pH. It appears that nature has built the cysteine molecule into the glutathione tripeptide to make the amino acid more soluble and allow it to have redox buffering activity in a living tissue environment. Glutathione also plays roles in catalysis, metabolism, signal transduction, gene expression and apoptosis. It is a cofactor for glutathione S-transferases, enzymes which are involved in the detoxification of xenobiotics, including carcinogenic genotoxicants, and for the glutathione peroxidases, crucial selenium-containing antioxidant enzymes (see Selenium). It is also involved in the regeneration of ascorbate from its oxidized form, dehydroascorbate. There are undoubtedly roles of glutathione that are still to be discovered.

Glutathione is an orphan drug for the treatment of AIDS-associated cachexia. It is thought that this disorder is due, in part, to oxidatively-stressed and damaged enterocytes. There is some evidence that although orally administered glutathione may not be absorbed into the blood from the small intestine to any significant extent, that it may be absorbed into the enterocytes where it may help repair damaged cells. Glutathione in one form or another is the subject of some medicinal chemistry research and some clinical trials. For example, an aerosolized form of glutathione is being studied in AIDS and cystic fibrosis patients. Glutathione, the principal antioxidant of the deep lung, appears to be diminished in those with AIDS. Prodrugs of gamma-L-glutamyl-L-cysteine are being evaluated as anticataract agents.

Glutathione (reduced) is known chemically as N-(N-L-gamma-glutamyl-L-cysteinyl)glycine and is abbreviated as GSH. Its molecular formula is C10H17N3O6S and its molecular weight is 307.33 daltons. Glutathione disulfide is also known as L-gamma-glutamyl-L-cysteinyl-glycine disulfide and is abbreviated as GSSG. Its molecular formula is C20H32N6O12S2.