Adaptive characteristics of urea cycle enzymes in the rat.

The response of the mammal to varying dietary protein intake under conditions in which amino acid and energy requirements are adequately satisfied is a form of adaptation involving the utilization of varying proportions of carbohydrate and amino acids as sources of energy, and is therefore analogous to the adaptation seen in bacteria on change in form of energy source (1). The amino nitrogen resulting from the utilization of amino acids for energy requirements is excreted largely as urea. This paper deals with investigations into the mechanisms by means of which the rate of urea synthesis is altered in response to differences in dietary protein consumption. Previous studies of the effects of dietary protein on rat liver arginase have demonstrated correlations between the levels of enzyme activity and dietary protein (24). This suggests that an increase in enzyme activity may be one factor in adaptation to varying dietary protein intake. With the recent characterization of the enzymatic steps involved in urea synthesis, largely by Ratner, Petrack, and Anslow (5-7), and by Cohen et al. (8, 9), specific assays have become available for the other enzymes involved in the synthesis of urea. Therefore, the relationships of urea cycle enzymes to dietary protein have been re-evaluated by studying all enzymes of the pathway leading from ammonia to urea, i.e. carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate cleavage enzyme, and arginase. This report will present studies on (a) relationships of dietary protein to urea cycle enzymes, glutamic-aspartic transaminase, glutamic-alanine transaminase, and lactic, glutamic, malic, and glucose g-phosphate dehydrogenases; (b) time courses of change in urea cycle enzymes after abrupt changes in levels of protein consumption; and (c) purification and characterization of arginase and ornithine transcarbamylase from animals with differing enzyme activities. The results indicate that adaptation to differing consumption of protein involves changes in activities of all urea cycle enzymes in the liver. The quantitative relationships between dietary protein and enzyme levels suggest that adaptation can be accounted for largely on the basis of differences in the levels of enzyme activity. Purified preparations of arginase and ornithine transcarbamylase from animals with differing enzyme activities have similar physiochemical and kinetic characteristics, indicating that adaptation is associated with differences in the actual content of specific enzyme protein.