INTERRELATIONSHIP BETWEEN UREOGENESIS AND PROTEIN-SYNTHESIS IN ISOLATED RAT-LIVER CELLS

The relationship was studied between urea synthesis and protein synthesis in isolated hepatocytes obtained from fasted rats. 1. 1. Addition of a physiological mixture of amino acids, in which arginine was replaced by ornithine, considerably increased ureogenesis and protein synthesis above the endogenous rates. 2. 2. Cycloheximide inhibited protein synthesis by about 95% and stimulated urea synthesis by about 15% only (see Woodside, K.H. (1976) Biochim. Biophys. Acta 421, 70-79). 3. 3. In the presence of norvaline, when flux through the urea cycle was inhibited by about 65%, the intracellular arginine concentration increased several-fold, but there was no significant change in the rate of protein synthesis. Furthermore, increasing the concentrations of added amino acids had no effect on the intracellular level of arginine. Thus arginine is not rate limiting for protein synthesis under these experimental conditions. 4. 4. A group of 11 amino acids added at low concentrations stimulated protein synthesis considerably but had little effect on ureogenesis. 5. 5. It is concluded that protein synthesis proceeds independently of urea synthesis, the reason being that the rate of the former process is governed primarily by the availability of a group of exogenous amino acids that, at low concentrations, do not contribute significantly to urea synthesis. © 1979.