Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets.

Abstract

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...

Adaptation to a long term (4weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet

“…The lowest arginine concentrations were observed when the APF diet had been consumed for 4 weeks (P < 0.001), but interestingly the lowest concentration was observed during the fed period. Plasma citrulline values were similar to those previously reported in healthy subjects, 11,15 and did not change with the 4-week APF intake. Plasma leucine concentrations were variable.…”

“…There was a difference (P = 0.001) in plasma arginine fluxes, regardless of the tracer used, for the fast and fed state, as previously observed. 11,15 However, there was no difference in plasma arginine fluxes between weeks 1 and 4 of the control group. In the APF group receiving adequate intake during week 1, there was a difference (P < 0.001) in plasma arginine fluxes between fed and fasted state.…”

“…8,11 In contrast to the plasma concentrations of arginine, ornithine, proline, glutamate, aspartate and leucine which decreased during the fasted state, when adequate intake was given, plasma citrulline was higher (P > 0.05) during the fasted state at 1 and 4 weeks for the control and APF groups, and this is also consistent with previous data. 15 There was a significant effect of the 4-week APF diet on plasma amino acid concentrations. Plasma arginine, ornithine, proline and aspartate were significantly decreased (P > 0.001) during the fed and fasted states when the subjects received the 4-week APF dietary period.…”

“…Previously, we have studied the changes in whole body arginine metabolism over a shorter, 6-day arginine-free diet and observed that (i) arginine fluxes were reduced, especially during the fed period, (ii) net arginine synthesis was not influenced by an acute change in arginine intake, (iii) the rate of conversion of arginine to ornithine was markedly reduced, as was the rate of arginine oxidation, especially in the fed state. 11,12,15 In the present study we extended the period of dietary restriction to 4 weeks, including limiting the intakes of the major, immediate dietary precursors of arginine (proline, glutamate, and aspartate). Nevertheless, in qualitative terms, the response to a 4-week APF restriction appears to be similar to that following a 1-week restriction of dietary arginine alone.…”

“…14,15 The rate of 13 CO 2 release from 13 C-labeled arginine (arg ox) or rate of leucine oxidation (leu ox), based on measurement of plasma arginine and leucine enrichments, and 13 CO 2 output in expired air, was calculated as previously described. In calculating leucine oxidation the contribution made to 13 CO 2 output via the hydrolysis of [ 13 C]urea was assumed to be insignificant.…”