Glutathione metabolism in the pancreas compared with that in the liver, kidney, and small intestine.
The pancreas plays a major role, along with the kidney, liver, small intestine, and several other organs, in glutathione (GSH) metabolism, as evidenced by the large concentration of GSH in the pancreas, its rapid turnover rate, and the presence, at significant levels, of various enzymes involved in GSH metabolism. The pancreas appears to obtain much of the cysteine that is required for both GSH and protein synthesis by hydrolyzing plasma GSH to its constituent amino acids and then transporting cysteine into the cells. GSH hydrolysis is accomplished by the ectoenzymes gamma-glutamyl transferase (GGTase) and aminopeptidase N, both of which are present in the pancreas. Only the kidney has a greater GGTase activity. Although pancreatic GSH synthesis has not been directly demonstrated, pancreatic secretory protein synthesis is substantial, and these proteins contain significant amounts of cysteine as disulfides. The pancreas also contains significant levels of protein disulfide isomerase, glutathione peroxidase, and NADPH:GSH oxidoreductase. Protein disulfide isomerase, using oxidized glutathione generated by glutathione peroxidase, is important in the formation of disulfide bonds in secretory proteins in the pancreas. No other organ has a higher specific activity of protein disulfide isomerase. By analogy with kidney and liver, the pancreas presumably exhibits a rapid apical secretion of GSH. The purpose of this apical secretion is unknown in the kidney. In the liver, it is important in bile secretion. The large GGTase activity of apical plasma membranes in the pancreas is likely to be instrumental in the hydrolysis, and subsequent recovery of the constituent amino acids of apically secreted GSH, as occurs in the kidney and liver.
Githens
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Department of Biological Sciences, University of New Orleans, LA 70148.
D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D005723:gamma-Glutamyltransferase; D005978:Glutathione