Functional Pancreatic Damage Produced by Ethionine, and its Relation to Methionine Deficiency

Abstract

Rats were allowed to eat, for 5 days, a diet containing amino acids in the approximate amounts provided by 18% casein, and containing 0.1% of ethionine and zero, 0.2, 0.4 or 0.8% of methionine. On the 6th day they were fed the diet and a pancreatic enzyme stimulant (soybean trypsin inhibitor, SBTI) by stomach tube. After two hours or 22 hours, they were killed and the pancreas and intestinal contents analyzed for lipase, protease and amylase. Under normal dietary stimulation, ethionine caused enzymes to accumulate in the pancreas regardless of the level of methionine in the diet. With secretion enforced by SBTI, ethionine almost completely inhibited enzyme discharge when zero, or 0.2% of methionine was present. At 0.8% of methionine, the pancreas response to SBTI was nearly normal. Twenty-two hours after stimulation, ethionine with zero, 0.2 and 0.4% of methionine greatly inhibited renewal of pancreatic lipase and to a lesser extent amylase activity. Protease activity remained relatively unaffected by methionine. With 0.8% of methionine in the diet, lipase and protease activities increased to nearly normal, whereas amylase activity in the pancreas increased to twice that of the control group. An acute methionine deficiency caused a depression in enzyme activity secreted into the intestine, but apparently had no effect on pancreatic enzyme discharge. The results indicated that ethionine impaired pancreatic function by inhibiting secretion and quite probably synthesis of new enzyme protein. Although methionine eventually counteracted most of the effects of ethionine it took much more than could be accounted for by assuming that the analogue acted only as a specific methionine antagonist.