Studies on factors affecting the levels of urea cycle enzymes in rat liver.

It has been previously demonstrated that the hepatic level of each enzyme concerned with the biosynthesis of urea in the rat, i.e. carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinase, and arginase (see Ratner (1) and Cohen and Brown (2) for discussions of the enzymatic steps of urea biosynthesis and general problems of urea synthesis), bears a direct relationship to the rate of urea excretion, irrespective of whether urea excretion is altered by varying the protein intake of the diet (3), or by starvation (4). It has also been shown that the increased activities of two of these enzymes, ornithine transcarbamylase and arginase, produced by feeding a protein-rich diet, are in fact due to increases in specific, electrophoretically homogenous protein (3). The present report presents a series of studies designed to elucidate in more detail the nature of factors which may possibly control the levels of this series of enzymes. Specifically, the following questions have been asked. 1. Does corticosteroid administration, which has been shown to result in rapid and extensive increases in activities of liver tryptophan pyrrolase (5) and tyrosine-glutamate transaminase (6, 7), increase the levels of each of the urea cycle enzymes? Does the absence of functioning adrenal glands abolish the ability of urea cycle enzymes to increase in activity when a protein-rich diet is given? What effect does ethionine administration have on the increase of urea cycle enzymes produced by corticosteroid administration in rat liver? 2. Does the administration of a number of specific amino acids, including urea cycle substrates, either by diet or parenterally, alter the levels of urea cycle enzymes? 3. Does the withdrawal of arginine from the diet of growing rats lead to a pattern of enzyme changes characteristic of arginine repression as found for bacteria (8)? 4. To what extent do alterations in the steady state concentrations of urea cycle enzyme substrates, ornithine, arginine, and citrulline, occur during conditions of altered rates of urea excretion?