The fluxes of arginine and citruiline through plasma and the rate of conversion of labeled citrulline to arginine were estimated in two pilot studies (with a total of six adult subjects) and in a dietary study with five healthy young men. These latter subjects received an L-amino acid-based diet that was arginine-rich or arginine-free each for 6 days prior to conduct, on day 7, of an 8-hr (first 3 hr, fast; final 5 hr, fed) primed continuous intravenous infusion protocol using L- [guandno-93C]arginine, L-[5,5-2H2]citrulline, and L- [5,5,5-2H31leucine, as tracers. A pilot study indicated that citrulline flux was about 20% higher (P < 0.05) when determined with [ureido-13C]citrulline compared with [2H2Jcitruline, indicating recycling of the latter tracer. Mean citruilin fluxes were about 8-11 pmol kg'lhr'1 for the various metabolic/diet groups and did not differ significantly between fast and fed states or arginine-rich and arginine-free periods. Arginine fluxes (mean ± SD) were 60.2 ± 5.4 and 73.3 ± 13.9 jAmol kg"l hr'1 for fast and fed states during the arginine-rich period, respectively, and were significantly lowered (P < 0.05), by 20-40%, during the arginine-free period, especially for the fed state, where this was due largely to reduced entry of dietary arginine into plasma. The conversion of plasma citruiline to arginine approximated 5.5 ,umol*kg'l-hr-1 for the various groups and also was unaffected by arginine intake. Thus, endogenous arginine synthesis is not markedly responsive to acute alterations in arginine intake in healthy adults. We propose that argmine homeostasis is achieved largely via modulating arginine intake and/or the net rate of arginine degradation.The physiological needs by tissues and organs for arginine are met via the endogenous synthesis of arginine and/or arginine supplied by the diet. For the U.S. population the latter amounts to about 5.4 g daily per capita (1). The rates of endogenous arginine synthesis in the immature rat (2, 3), guinea pig (4), cat (5, 6), dog (7-9), chicken (10), rabbit (11), and pig (12) of nitric oxide (16) and of creatine and its participation as arginyl-tRNA in the process of ubiquitin-dependent protein degradation (17). Therefore, we have begun to use stableisotope tracer techniques to explore, noninvasively, kinetic and regulatory aspects ofarginine metabolism in adult human subjects (18,19). Here we report results of a study in young men who were given for 7 days an arginine-rich diet and then, for another 7 days, an arginine-free diet. Our kinetic model involves L-[guanidino-13C]arginine and L-[5,5-2H2]citrulline as tracers, to estimate plasma arginine and citrulline fluxes as well as the rate of transfer of plasma citrulline into the arginine pool. From the present findings, and our recent studies (19), we propose an integrative scheme of body arginine homeostasis and balance, which defines the metabolic basis for the conditional indispensability of dietary arginine under various pathophysiological conditions (1, 13, 14).
MATERIALS AND METHOD...