ABSTRACT
The thiol tripeptide glutathione (GSH) functions as an intracellular reductant and, in this way, plays an important protective role in conditions of oxidative stress or cell injury caused by a variety of chemicals. 1 , 2 During the course of the redox reactions, GSH is continuously oxidized to glutathione disulfide (GSSG) and rereduced by the enzymes GSH-peroxidase (EC 1.11.1.9) and GSSG reductase (EC 1.6.4.2), respectively. GSSG reductase uses reduced β-nicotinamide-adenine dinucleotide phosphate (NADPH) as a specific substrate and, in this way, the redox status of GSH is connected to that of NADPH and the cellular NADPH-generating systems. GSH may also be consumed nonenzymatically or in GSH/S-transferase (EC 2.5.1.18)-catalyzed reactions with a variety of electrophilic substrates. 3 Moreover, a continuous release of GSH and/or GSSG have been demonstrated in liver 4 , 5 and heart. 6 An active synthesis of new GSH from its precursor amino acids is thus required by the cells in order to retain a constant intracellular concentration. This release coincides in magnitude approximately with the γ-glutamyl transpeptidase (EC 2.3.2.2) activity of the tissue. This involves the so-called γ-glutamyl cycle, which is discussed in detail elsewhere in this book.
