The effect of ethionine on hepatic gluconeogenesis in the rat.

Abstract

Abstract 1. 1. The effect of ethionine on glucose formation from [2-14C]pyruvate in vivo was measured in female rats fasted for varing periods and was compared with the effects of ethionine on the activities of the four unique hepatic gluconeogenic enzymes, glucose-6-phosphatase (EC 3.1.3.9), fructose-1,6-diphosphatase (EC 3.1.3.11), pyruvate carboxylase (EC 6.4.1.1) and phosphoenolpyruvate carboxykinase (EC 4.1.1.32). The activities of pyruvate carboxylase and phosphoenolpyruvate carboxykinase were also measured in adipose tissue of ethionine-treated and control rats. 2. 2. Ethionine injection followed by fasting for 24, 48 and 72 h resulted in an increase in the liver lipid content, which returned to normal levels of 96–120 h after ethionine injection. The usual increase in hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activities induced by fasting was inhibited by the injection of ethionine. The activity of pyruvate carboxylase, although not increased by fasting, was reduced almost 50% by ethionine treatment. Fructose-1,6-diphosphatase activity was unaffected by ethionine. Adipose-tissue mitochondrial pyruvate carboxylase activity was not reduced by ethionine injection and the normal induction of phosphoenolpyruvate carboxykinase in this tissue by fasting for 48 h was not blocked by the administration of ethionine prior to fasting. 3. 3. Despite these effects of ethionine on the hepatic enzymes of the fasted rat, gluconeogenesis from pyruvate was not reduced by ethionine injection followed by a 48-h fast. The blood glucose concentration, although lowered 10% by fasting for 48 h was unaffected by ethionine injection. These findings suggest that activities of the four hepatic gluconeogenic enzymes do not limit the rate of glucose formation in the rat.