Metabolic fate of extrahepatic arginine in liver burn injury

Increased nitrogen loss in the form of urea is a hallmark of the metabolic aberrations that occur after burn injury. As the immediate precursor for urea production is arginine, we have conducted an investigation on the metabolic fate of arginine in the liver to shed light on the metabolic characteristics of this increased nitrogen loss. Livers from 25% total surface burn (n = 8) and sham burn rats (n = 8) were perfused in a recycling fashion with a medium containing amino acids and stable isotope labeled L-[¹⁵N₂-guanidino, 5,5-²H₂]arginine for 120 minutes. The rates of glucose and urea production and oxygen consumption were measured. The rate of unidirectional arginine transport and the intrahepatic metabolic fate of arginine in relation to urea cycle activity were quantified by tracing the disappearance rate of the arginine tracer from and the appearance rate of [¹⁵N₂]urea in the perfusion medium. Perfused livers from burned rats showed higher rates of total urea production (mean ± SE, 4.471 ± 0.274 v 3.235 ± 0.261 μmol.g dry liver^-1.min^-1; P < .01). This was accompanied by increased hepatic arginine transport (1.269 ± 0.263 v 0.365 ± 0.021 μmol.g dry liver^-1.min^-1) and an increased portion of urea production from the transported extrahepatic arginine (12.9% ± 2.9% v 3.5% ± 0.4%, P < .05). The disposal of arginine via nonurea pathways was also increased (0.702 ± 0.185 v 0.257 ± 0.025 μmol/g dry weight^-1/min^-1; P < .05). We propose that increased inward transport and utilization of extrahepatic arginine by the liver contributes to the accelerated urea production after burn injury and accounts, in part, for its conditional essentiality in the nutritional support of burn patients.