The physiological consequences of glutathione variations
Dr. Albrecht Wendel1992, Life Sciences
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Abstract
~,mrnRry The major low molecular weight thiol inside cells, the tripeptide glutathione (GSH), is of importance for protection of the cell against oxidative challenge, for thiol homeostasis required to guarantee basic functions, and for defence mechanisms against xenobiotics. Since the pathophysiological significance of a perturbed GSH status in human disease is less clear, this review evaluates the consequences of/n viuo variations of GSH. Owing to intracellular GSH concentrations above 2 mM depletion of GSH as such has little metabolic consequences unless an additional stress is superimposed. The kinetic properties of GSH-dependent enzymes imply that loss of up to 90% of intraceUular GSH may still be compatible with cellular integrity. Mitochondrial GSH, which accounts for about 10% of total cellular GSH, may define the threshold beyond that toxicity commences. Thus, in cases of severe GSH-depletion a substitution of GSH as a therapeutic measure seems justified. Such a severe depletion of GSH has been described for some diseases such as liver dysfunction, AIDS or pulmonary fibrosis. I. Scope The intracellular redox balance of mammalian cells is maintained by a homeostatic mechanism which links small pools of coenzymes and cofactors to a large redox buffer with common chemical properties, i.e. the thiol system. The overwhelming part of intra-as well as extracellular soluble thiols is represented by the tripeptide glutathione (GSH) which occurs in any eukaryotic cell in high concentrations, i.e. 2-10 retool/1. The intactness of this glutathione system is essential for maintainment of physiological functions. The continuing research interest in glutathione is documented by a publication rate of two scientific papers per day with an increasing frequency of monographies published [Cited in ref. [1] and [2]).
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