Conversion of glutathione to glutathione disulfide by cell membrane-bound oxidase activity.

Abstract

An apparently specific glutathione oxidase activity is present in renal cortex, epididymal caput, jejunal villus tip cells, choroid plexus, and retina (but not in liver). The activity is membrane-bound and is localized on the luminal surface of the brush border membranes of the kidney and jejunum. The distribution and localization of the oxidase are similar to those of 'y-glutamyl transpeptidase, suggesting that there is a significant relationship among the translocation of intracellular glutathione, the extracellular oxidation of glutathione to glutathione disulfide, and the reactions of the y-glutamyl cycle. Thus, both glutathione present in the blood plasma and intracellular glutathione translocated to the cell surface are accessible to oxidation and transpeptidation. Acceptor substrates of the transpeptidase (e.g., L amino acids) promote transpeptidation and decrease oxidation of glutathione. Conversion of glutathione to glutathione disulfide is followed by utilization of the latter compound by 'y-glutamyl transpeptidase and dipeptidase. Although intracellular oxidation of glutathione to glutathione disulfide is readily reversed by the action of glutathione reductase, glutathione disulfide formed extracellularly cannot be reduced; instead, it undergoes hydrolytic and transpeptidation reactions leading to y-glutamyl amino acid and amino acid products which may be recovered by being transported into the cell. Recent studies on the metabolism of glutathione have provided new evidence that the reactions of the y-glutamyl cycle (1) occur in vivo (2-5) and that translocation of glutathione across renal cell membranes is a discrete step in the cycle (6, 7). The available data also indicate that intracellular glutathione is translocated out of other cells-e.g., liver (6, 8) and lymphoid cells (7). Cells that have relatively little -y-glutamyl transpeptidase activity translocate glutathione into the blood plasma whereas, in renal cells, intracellular glutathione is translocated to membrane-bound 'y-glutamyl transpeptidase. Normally, little, if any, glutathione is found in the urine, and the blood plasma levels of glutathione are maintained at extremely low levels. However, after administration of a potent 'y-glutamyl transpeptidase inhibitor to mice, the amount of glutathione excreted in the urine increased substantially and the blood plasma level of glutathione also increased appreciably; most of the glutathione found in the urine was in the form of glutathione disulfide (6). More than half of the glutathione of blood plasma is also present in the disulfide form. These observations are consistent with the function of a system or systems that mediate the oxidation of extracellular glutathione.Some years ago, Elvehjem and collaborators (9, 10) found that mouse kidney homogenates catalyze oxygen-dependent conversion of glutathione to glutathione disulfide and that this reaction is inhibited by cyanide. These workers also found that kidney exhibits much higher glutathione oxidase activity than does liver. Recent...

γ-Glutamyl transpeptidase-catalyzed synthesis of naturally occurring flavor enhancers

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Role of Glutaredoxin-Mediated ProteinS-Glutathionylation in Cellular Nitroglycerin Tolerance

“…This is possibly mediated by the abundant expression of ␥-glutamyl transpeptidase on the apical membrane of these cells when confluent (Rabito et al, 1984). This enzyme plays a crucial role in the ␥-glutamyl cycle and catabolizes GSH and GSSG into intermediate peptides or amino acids that can be taken up by cells (Jones et al, 1979;Tate et al, 1979). Once in the cells, these peptides and amino acids can be used to synthesize GSH and GSSG (Griffith and Meister, 1979), thus leading to an increase in our system.…”

Assessment of the kidney function in maintenance of plasma glutathione concentration and redox state in anaesthetized rats

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