This ubiquitous tripeptide (Ly-glutamyl-L-cysteinylglycine), usually the most prevalent intracellular thiol, is now known to function directly or indirectly in many important biological phenomena, including the syn thesis of proteins and DNA, transport, enzyme activity, metabolism, and protection of cells. The multifunctional properties of glutathione are reflected by the growing interest in this small molecule on the part of investigators of such diverse subjects as enzyme mechanisms, biosynthesis of macromolecules, intermediary metabolism, drug metabolism, radiation, cancer, oxygen toxicity, tr nsport, immune phenomena, endocrinology, environmental toxins, and aging.

This chapter is concerned with current progress in unraveling the biochemical bases of the physiological roles of this important compound. Detailed information is now available about glutathione synthe i and its metabolism by the reactions of the y-glutamyl cycle, and its function in reductive processes that are essential for the synthesis (and the degradation) of proteins, formation of the deoxyribonucleotide precursors of DNA, regulation of enzymes, and protection of the cell against reactive oxygen compounds and free radicals. In addition, glutathione is a coenzyme for several reactions; it conjugates with foreign compounds (eg drugs) and with compounds formed in metabolism (eg estrogens, prostaglandins, leukotrienes), and thus participates in their metabolism. An important recent finding is that cellular turnover of glutathione is associated with its transport, in the form of GSH, out of cells. The functions of such GSH transport include formation by membrane-bound y-glutamyl transpeptidase of y-glutamyl amino acids, which can be transported into certain cells, and thus serve as one mechanism of amino acid transport. Transported GSH probably also functions in reductive reactions that may involve the cell membrane and the immediate environment of the cell. In the mammal, such transported GSH may enter the blood plasma and be transferred to other cells. Glutathione thus appears to be a storage form and a transport form of cysteine.