Glutathione: Physiological and Clinical Relevance

Glutathione (GSH), the most abundant intracellular low molecular weight thiol, has diverse physiological roles, and altered GSH status has been implicated in a number of chronic, acute, and age-related diseases, as well as the aging process itself. Its function as an antioxidant and determinant of cellular redox potential is crucial both for protection from reactive oxygen species as well as a signaling molecule involved in cellular proliferation, cell cycle regulation, and apoptosis. It is also an important thiol buffer, maintaining sulfhydryl groups in their reduced form, an additional mechanism for cellular signaling.Glutathione has also emerged a key modulator of xenobiotic toxicity, most notably the persistent organic pollutants which are associated with many diseases of impaired metabolic activity, including diabetes, obesity, and cardiovascular disease. γ-glutamyl transpeptidase (GGT), an enzyme critical to the catabolism of GSH and its conjugates, appears to be an important biomarker for xenobiotic exposure, and for increased GSH demand. We review the physiological functions of glutathione, the limiting factors for its synthesis, as well as its clinical relevance, with particular emphasis on detoxification of environmental pollutants. We also review therapeutic approaches for enhancing GSH status.