Regulation of carbamoyl-phosphate synthase II.

Evidence was provided that in rat liver synthase II activity, amount and turnover were regulated primarily by insulin. When rats were starved, synthase II activity and the immunotitratable enzyme amount markedly decreased; refeeding restored enzyme activity and amount to normal range. The changes in activity and amount were paralleled with alterations in the level of circulating insulin in the plasma. When starved rats were treated with anti-insulin serum before and during refeeding, the animals consumed the food, but the rise in synthase II activity was prevented. In diabetic rats, the activity and amount of synthase II in the liver markedly decreased and insulin treatment restored them to normal range. Actinomycin treatment prevented the refeeding and the insulin-induced rise in synthase II activity and amount. Study of the turnover of synthase II showed that in starvation the rate of synthesis decreased and refeeding restored the enzyme synthetic and degradation rates to normal range. In the diabetic rat, synthase II synthetic rate markedly decreased, and the degradation rate increased. Insulin returned the synthetic and catabolic rates to normal livers. In rapidly growing rat hepatoma 3924A, synthase II activity and amount were elevated 9- to 10-fold. Turnover studies showed that the synthetic rate in hepatoma 3924A was approximately 10-fold higher than that of normal liver. The catabolic rates of synthase II were similar in the liver and hepatoma. Thus, the increased activity and amount of synthase II in the hepatoma was due primarily to an increased rate of enzyme biosynthesis. Evidence was presented that in starvation and diabetes and on refeeding and insulin administration there is very little or no change in the enzymic activity, amount and turnover of hepatoma synthase II. The marked contrast between the turnover rate of hepatoma 3924A synthase II activity and that of the normal liver enzyme in starvation and in diabetes is under investigation. This overview of the behavior of activity, amount and turnover of synthase II in liver and hepatoma 3924A provides evidence of the important role of insulin in regulation of liver synthase II and of the apparent lack of responsiveness of the hepatoma enzyme to insulin concentrations. The precise details of the experimental procedures and the enzymic results will be published elsewhere.