GLUTATHIONE SYNTHESIS IN THE EXOCRINE PANCREAS

Glutathione is essential for cellular cytoprotection, and in the exocr ine pancreas, it is required for digestive enzyme synthesis. The purpo se of these studies was to measure the capacity of the exocrine pancre as to synthesize glutathione, determine whether the pancreatic transsu lfuration pathway has a role in providing cysteine needed for glutathi one synthesis, and determine whether the glutathione synthetic capacit y of the pancreas responds ro pathologically relevant stresses. The ac tivity of gamma-glutamylcysteine synthetase, the key regulatory enzyme for glutathione synthesis, was 3.56 +/- 0.29 mU/mg protein in the pan creas of fed rats, compared to 31 +/- 4 in the liver and 116 +/- 5 in the kidney. Studies using dispersed rat pancreatic acinar cells showed that the exocrine pancreas synthesizes glutathione from precursor ami no acids and that the transsulfuration pathway is functionally intact in the pancreas and may serve as an important source of pancreatic cys teine. in mice, pancreatic gamma-glutamylcysteine synthetase activity was induced 37% by corn oil, 77% by ethanol, and 88% by both treatment s. Thus, the glutathione synthetic capacity of the pancreas is quantit atively less than that of the kidney or liver, but its key regulatory enzyme responds dynamically to pathologically relevant metabolic stres ses, suggesting that glutathione is a key pancreatic cytoprotectant.