The biochemical pathology of ethionine-lnduced pancreatic damage: Ethionine incorporation into proteins, and ATP levels in pancreas of rats

Abstract

Two biochemical mechanisms of possible pathogenetic significance in injury of cells by ethionine are synthesis of abnormal proteins by ethionine incorporation, and induction of ATP deficiency. These hypotheses were evaluated in relation to ethionine-in-duced pancreatic damage in rats. Ethionine incorporation into pancreatic protein was found to conform to the pattern which has been reported for several natural amino acids. Incorporation continued for at least 9 hours following a dose of 0.5 g per kg, apparently because a significant level of free ethionine persisted. The pancreas did not appear to have any unique tendency to incorporate ethionine into structural proteins when compared with liver and kidney, and therefore the results do not suggest that formation of abnormal proteins is of special significance in the pancreas. S-adenosylethionine accumulation and ATP deficit were demonstrated in pancreas 24 hours following single doses of ethionine (1 g per kg). However, at a lower dose which was adequate to produce severe pancreatic damage, there was no decrease in ATP in the pancreas. It therefore appears that the ethionine-induced pancreatic lesion cannot be attributed to ATP deficiency.