Renal arginine metabolism

Kidneys of normal animals remove citrulline from blood and convert it, stoichiometrically to arginine. This citrulline arises from the intestinal metabolism of glutamine. This intestinal-renal pathway constitutes the major endogenous source of arginine. The objectives of the present studies are to determine the location of arginine synthesis in kidney and its response to citrulline concentrations in vitro and in vivo and to different arginine or protein intakes in rats. -- Investigations on the localization of enzymes of arginine synthesis (argininosuccinate synthetase and argininosuccinate lyase) and of breakdown (arginase and ornithine aminotransferase), revealed that the enzymes of arginine synthesis are exclusively present in the cytosol of the cells of the proximal convoluted tubule and that of arginine degradation are enriched in other kidney regions. -- Arginine synthesis from citrulline in isolated kidney cortical tubules was found to be highly sensitive to citrulline concentrations in the physiological plasma range (0.06 mM), suggesting that renal arginine synthesis in vivo could be regulated by circulating citrulline levels. Thus, in studies on renal arginine synthesis in vivo, it was found that kidneys of rats infused with citrulline (saline-infused, as controls) responded to the elevated plasma citrulline levels by increasing its uptake and producing increased quantities of arginine. -- In studies with rats fed different levels of arginine (0.0, 0.5, 2.0%) or protein (5, 12 and 50%) for 1 week, it was found that the renal uptake of citrulline and release of arginine and also circulating citrulline levels were similar in all these animals. This suggested that renal arginine synthesis is independent of dietary arginine or protein intake. The results suggest that availability of citrulline is a limiting factor for renal arginine synthesis in rats.