Arginine metabolism in mammals

Arginine (ARG), a semiessential amino acid, is taken up by cells using the y+ transport system. ARG synthesis occurs from citrulline mainly in the liver and in the kidney. ARG is metabolized either in ornithine and urea mainly in the liver and the intestine or in citrulline and nitric oxide (NO•) in a large number of cell types. Ornithine derived from arginine can be metabolized in citrulline (in the context of the urea cycle), in glutamate or in polyamines. Arginine taken up by the intestine is transformed into citrulline which is poorly taken up by the liver but mainly by the kidney. In the kidney, citrulline is transformed into arginine and subsequently released for peripheral tissues. Intestinal transformation of arginine into citrulline plays a keyrole in the metabolic adaptation to high/low protein diets. In the liver, arginine metabolism plays a pivotal role in the urea cycle, the rate of which is conditioned not only to metabolize extranitrogen, but also to maintain the acid-base homeostasis. Immune cells exhibit the ability to synthesize both polyamines and NO• which are potent immunomodulators. The modulation and balance between these two pathways remain to be elucidated. In the context of clinical nutrition, the use of ARG supplemented diets may be advocated while keeping in mind that in severe injury with organ failure such regimens could be detrimental. (J. Nutr. Biochem. 6:402-403, 1995.)