glutathione

Glutathione is a tripeptide composed of glutamate, cysteine and glycine.

Glutathione is present in millimolar concentrations in most mammalian cells and it is involved in several fundamental biological functions, including free radical scavenging, detoxification of xenobiotics and carcinogens, redox reactions, biosynthesis of DNA, proteins and leukotrienes, as well as neurotransmission/neuromodulation.

Glutathione is metabolised via the gamma-glutamyl cycle, which is catalyzed by six enzymes. In man, hereditary deficiencies have been found in five of the six enzymes.

Function

 In lungs

• The most important extracellular antioxidant in the lung is glutathione (GSH). The epithelial lining fluid of normal lungs contains very high concentrations of this tripeptide, about 100 times higher than that found in the extracellular fluid of many other tissues.
• How these high extracellular GSH levels are established and the mechanisms for increases (e.g. smokers) or decreases (e.g. lung fibrosis) are still unknown, but more insight into the regulation of GSH turnover in type II pneumocytes has recently become available.
• GSH is, in fact, an important vehicle for stabilizing, detoxifying and transferring cysteine;
• cysteine is the rate-limiting substrate for GSH synthesis, especially under conditions of oxidative stress;
• various transport systems exist for the uptake of the constituents of GSH, of which gamma-glutamyltransferase appears to be important;
• intracellular GSH levels of the type II cells are governed by different factors, including, probably, the extracellular redox state;
• a more reduced extracellular redox state appears to favour GSH efflux, whilst an oxidized state leads to retention of GSH inside the cell.

See also

 glutathione cycle

References

 Ristoff E, Larsson A. Inborn errors in the metabolism of glutathione. Orphanet J Rare Dis. 2007 Mar 30;2:16. PMID: 17397529

 van Klaveren RJ, Demedts M, Nemery B. Cellular glutathione turnover in vitro, with emphasis on type II pneumocytes. Eur Respir J. 1997 Jun;10(6):1392-400. PMID: 9192948