The regulation of hepatic glutathione.

Glutathione (GSH) is a peptide composed of glutamate, cysteine, and glycine that exists in thiol·reduced (GSH) and disulfide-oxidized (GSSG) forms. GSH has been the subject of intense interest in the past decade and numerous symposia and reviews have been written about its function and regulation since 1 980 ( 1 -7). We propose to review some of the recent exciting developments in this field, with a particular focus on the regulation of hepatic GSH. We will not exhaustively review the literature and therefore apologize for inadvertent or intentional omissions. We hope to bring a personal and different perspective to this subject. A few words about the functions of GSH will focus on the importance of elucidating the physiology and biochemistry of the regulation of this vital substance . GSH is a fairly ubiquitous substance in aerobic life forms and tissues and generally exists in millimolar concentrations . The liver is among the organs with the highest content of GSH. The heterogeneity of GSH content in tissues has been observed. Thus , periportal hepatocytes may contain approximately twice the centrilobular concentration, enterocytes at the villus tip have a higher content than the crypts, and proximal tubular cells of kidney have more GSH than other parts of the nephron (8-1 0) . GSH plays a critical role in detoxification reactions. It is a specific substrate for GSH peroxidase ( 1 1 ) and GSH S-transferases ( 12), and it participates in microsomal peroxidase and radical scavenging reactions ( 1 3, 14). In this regard, probably the key function of GSH is reducing hydrogen peroxide (H202), a reaction catalyzed by GSH peroxidase. H202 production is a by-

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