Influence of pancreatic hormones on enzymes concerned with urea synthesis in rat liver

1. The activities of enzymes of the urea cycle carbamoyl phosphate synthetase, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinase (these last two comprising the arginine-synthetase system) and arginase] have been measured in control, alloxan-diabetic and glucagon-treated rats. In addition, measurements were made on alloxan-diabetic rats treated with protamine–zinc–insulin. 2. Treatment of rats with glucagon for 3 days results in a marked increase in the activities of three enzymes of the urea cycle (carbamoyl phosphate synthetase, argininosuccinate synthetase and argininosuccinase). The pattern of change in the alloxan-diabetic group is very similar to that of the glucagon-treated group, although the magnitude of the change was much greater. 3. Comparison was made of the actual and potential rate of urea synthesis in normal and diabetic rats. In both groups the potential rate of urea production, as measured by the activity of the rate-limiting enzyme, argininosuccinate synthetase, slightly exceeds the actual rate of synthesis by liver slices in the presence of substrates. The relative activities of the actual and potential rates were similar in the two groups of animals, this ratio being 1:0·70. 4. In the alloxan-diabetic rats treated with protamine–zinc–insulin for 2·5 or 4 days there was a marked increase in liver weight. This was associated with a rise in the total hepatic activity of the urea-cycle enzymes located in the soluble fraction of the cell (the arginine-synthetase system and arginase) after 2·5 days of treatment. After 4 days of treatment the concentration of these enzymes/g. of liver decreased, and the total hepatic content then reverted to the untreated alloxan-diabetic value. 5. No effects of glucagon or of insulin in vitro could be found on the rate of urea production by liver slices. 6. The present results are discussed in relation to how far this pattern of change is typical of conditions resulting in a high urea output, and comparison has been made with other values in the literature.