Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal

Abstract

Arginine serves multiple roles in the pathophysiological response to burn injury. Our previous studies in burn patients demonstrated a limited net rate of arginine de novo synthesis despite a significantly increased arginine turnover (flux), suggesting that this amino acid is a conditionally indispensable amino acid after major burns. This study used [15N2-guanidino-5,5-2H2]arginine and [5-13C]ornithine as tracers to assess the rate of arginine disposal via its conversion to and subsequent oxidation of ornithine; [5,5-2H2]proline and [5,5,5-2H3]leucine were also used to assess proline and protein kinetics. Nine severely burned patients were studied during a protein-free fast ("basal" or fast) and total parenteral nutrition (TPN) feedings. Compared with values from healthy volunteers, burn injury significantly increased 1) fluxes of arginine, ornithine, leucine, and proline; 2) arginine-to-ornithine conversion; 3) ornithine oxidation; and 4) arginine oxidation. TPN increased arginine-to-ornithine conversion and proportionally increased irreversible arginine oxidation. The elevated arginine oxidation, with limited net de novo synthesis from its immediate precursors, further implies that arginine is a conditionally indispensable amino acid in severely burned patients receiving TPN.

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

“…Our tentative conclusion concerning the dietary dispensability of arginine applies only to healthy subjects and with nutritional balance as an endpoint; we have previously concluded that a source of dietary arginine is required in severely stressed patients 16 and so in this case arginine is a conditionally indispensable amino acid.…”

“…8 The 13 C retention factor for estimating arginine oxidation was obtained from 6 healthy subjects receiving a constant infusion of L-[5-13 C]glutamic acid. 16 These studies gave a fractional recovery of 13 CO 2 of 0.40 and 0.52, respectively, for fasting and fed states in healthy subjects. L-[5-13 C]glutamic acid was used to determine fractional retention of 13 C, because its 13 C carbon is a more direct precursor for estimation of arginine oxidation, than bicarbonate or acetate.…”

Amino acid requirements in inflammatory states

“…Such production should be accompanied by a higher rate of arginine and glutamine fluxes. As mentioned above, the synthesis of ornithine from arginine is increased in burn patients (Yu et al 2001). From the few studies on arginine metabolism in patients, it appears that arginine is mainly lost by degradation in the urea cycle.…”

“…Arginine is also produced by the intestine from glutamate (Reeds 2000). In humans, use of plasma kinetics has provided an unclear picture to whether endogenous arginine synthesis is modified in inflammatory states (Castillo et al 1995;Yu et al 1995aYu et al , 2001). In contrast, arginine production by the portal drained viscera was increased during endotoxemia in pigs (Bruins et al 2000).…”

“…Therefore, it is unlikely that such synthesis is of sufficient magnitude to be of nutritional concern. In contrast, the synthesis of ornithine from arginine is increased, both in relative and absolute amounts, in burn patients (from 23 to 38% of arginine flux; Yu et al 2001). Moreover, it has been shown that glucocorticoids are important factors in mediating the increase of arginine degradation in enterocytes of weaning pigs (Flynn and Wu 1997).…”