We measured plasma arginine and leucine kinetics and rates of urea production (appearance) in 12 severely burned patients (mean body surface burn area, 48%) during a basal state (low-dose intravenous glucose) and while receiving routine, total parenteral nutrition ([TPN] fed state) including an l-amino acid mixture, supplying a generous level of nitrogen (mean, 0.36 g N · kg-1 · d-1). The two nutritional states were studied in random order using a primed 4-hour constant intravenous tracer infusion protocol. Stable-nuclide-labeled tracers were l-[guanidino-13C]arginine, l-[1-13C]leucine, [18O]urea, and NaH13CO3 (prime only), with blood and expired air samples drawn at intervals to determine isotopic abundance of arginine, citrulline, ornithine, α-ketoisocaproate ([KIC] for leucine), and urea in plasma and 13CO2 in breath. Results are compared with data obtained in these laboratories in healthy adults. Leucine kinetics (flux and disappearance into protein synthesis) indicated the expected higher turnover in burn patients than in healthy controls. Mean leucine oxidation rates are also higher and compared well with values predicted from urea production rates, provided that urea nitrogen recycling via intestinal hydrolysis is taken into account. The plasma urea flux was also higher than for normal subjects. Arginine fluxes as measured in the systemic whole body, via the plasma pool, were correspondingly higher in burned patients than in healthy controls and were in good agreement with values predicted from leucine-KIC kinetics. However, systemic whole-body arginine flux measured via the plasma pool was only 20% of the arginine flux estimated from the urea flux plus the rate of protein synthesis. This finding is strong evidence that there is a significant synthesis of arginine (probably via recycling of ornithine) occurring in a sequestered pool (presumably in the hepatocyte) that is not in close communication with the plasma pool. Further, these data for plasma arginine flux suggest that the net rate of arginine degradation is increased in burn trauma, while there also appears to be a continued low and possibly unchanged net rate of de novo arginine synthesis contributing arginine to the plasma pool. This interpretation leads to the conclusion that there are at least two significant metabolic pools of arginine, one highly sequestered related specifically to urea synthesis and the other a systemic pool in equilibrium with the plasma. Because the hepatic urea-arginine cycle does not contribute substantially to making arginine available for protein synthesis, we propose from these findings that arginine is a conditionally essential (indispensable) amino acid in the nutrition of severely burned patients and that an exogenous arginine source is needed to maintain arginine balance.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism