1. Measurements were made, at 6 h intervals, of urinary nitrogen output and of the activity of some hepatic enzymes in the rat during adaptation from one level of dietary protein to another. The enzymes measured were arginase (EC 188.8.131.52), argininosuccinate lyase (EC 184.108.40.206), argininosuccinate synthetase (EC 220.127.116.11), glutamate dehydrogenase (EC 18.104.22.168) and alanine and aspartate aminotransferases (EC 22.214.171.124 and EC 126.96.36.199).
2. Completeness of urine collection, which was essential for these experiments, was checked by recovery of injected [131I]iodide.
3. When the dietary protein content was reduced from 135 to 45 g casein/kg, the urinary N output and the activities of the hepatic enzymes reached their new steady-state levels in 30 h. The reverse adaptation, from 45 to 135 g casein/kg, was also complete in 30 h.
4. The rate of change of enzyme activity and the final activity as percentage of initial activity were very similar for all six enzymes, suggesting a common control mechanism. The calculated half-lives of the enzymes were of the order of 7 h, which is very much shorter than those found by previous workers.
5. There was no simple relationship between the activity of the urea cycle enzymes and the amount of N excreted. When an equal amount of gelatin was substituted for casein the N output was doubled but there was no change in the activity of the liver enzymes.
6. The results suggest that the activity of the urea cycle enzymes depends in part on the amount of N available for excretion after the demands for synthesis have been met. The enzymes, however, appear to be present in excess so that an increased N load was not necessarily accompanied by an increase in enzyme activity.