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This paper reviews studies on a) biosynthesis and degradation of glutathione, b) regulation of glutathione levels, and c) transport of glutathione. Glutathione levels in tissues and cells are regulated by a feed back inhibition of γ-glutamyl cysteine synthetase by GSH. Glutathione is conjugated with numerous electrophiles by a catalytic reaction of glutathione S-transferase and the reaction product, glutathione S-conjugate also plays an important role in the regulation of glutathione levels. The S-conjugate releases the feed back inhibition of γ-glutamyl cysteine synthetase by GSH. The S-conjugate also inhibits glutathione reductase and this brings about changes in GSH/GSSG ratio. GSSG efflux occurs in two different processes such as high affinity (low Km) and low affinity (high Km) processes. The glutathione S-conjugate competes the low affinity process, indicating that GSSG and glutathione S-conjugate are transported by the same carrier system. These processes are energy-dependent and requires ATP. The GSSG efflux is inhibited by NaF. The GSSG-stimulated ATPase is present in erythrocytes, heart muscle as well as canalicular or basolateral membranes of the liver. Investigation on efflux of GSSG and glutathione S-conjugate indicates that a transport mechanism analogous to that of erythrocytes exists in various cells and tissues. The efflux of these materials is considered to be an extracellular parameter to assess oxidative stress in cells and tissues.
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