Arginine (Arg) Turnover and Oxidation in Neonates Receiving Total Parenteral Nutrition (TPN) • 1497

Abstract

In human, Arg is generally considered a dispensable amino acid. However, it has been proposed that Arg may be an indispensable amino acid in neonates after an increase in blood ammonia level was observed when arginine was removed from amino acid solution used in parenteral nutrition.Method: In order to estimate net de novo synthesis, in vivo, in neonates fed parenterally, I evaluated Arg and citrulline (Cit) metabolism measuring respective plasma amino acids fluxes and whole-body rate of Arg oxidation based on a single pool model (Beaumier, 1995). Rate of conversion of plasma Cit to Arg was also measured using the Clarke and Bier equation (1982). Protein turnover was also measured usingα-ketoisocaproic acid (α-KIC) as representative metabolite of leucine metabolism (Matthews 1982). Experiments: After being on TPN for 4-5 days, providing 3 gm of protein/kg/day and a minimum of 120 kcal/kg/day, a known primed constant infusion of [5-13C] Arg,[15N2-guanidino] Arg, [5,5-2H2, 13C-ureido] Cit and [5,5,5-2H2] leucine was given for five hours. Blood and breath samples were taken once before and twice, at 30 minute intervals, at the end of the infusion. Expired 13CO2 was corrected for under-recovery of 13C-label from infused [5-13C] ornithine. Isotopic abundance of amino acids and α-KIC was measured by GC/MS as methyl ester-TFA and t-BDMS derivatives, respectively. Results: Under these conditions, plasma Arg and Cit flux were measured at 209 ± 17 and 37± 3 μmol/kg/h, respectively. Arg oxidation was measured at 76± 6 with a dietary Arg intake was 69 ± 10 μmol/kg/h. Rate of conversion of plasma Cit into Arg was 15 ± 3 μmol/kg/h. The small excess in Arg oxidation and the low rate of conversion support the concept that neonates have a very limited rate of Arg de novo synthesis. Leucine appearance from protein breakdown was 141 ± 18 μmol/kg/h, which represents 9.4 ± 1.2 g/kg/day of protein. Conclusion: Net rate of endogenous Arg synthesis is measurable in neonates receiving TPN but remains relatively small in comparison to the whole-body turnover of the amino acid. These results are consistent with a limiting capacity for neonates to synthesize arginine supporting the recommendation that Arg is an indispensable amino acid in neonates fed a parenteral solution.