|MARINI, JUAN - Children'S Nutrition Research Center (CNRC)|
|PREMKUMAR, MURALI - Baylor College Of Medicine|
|DIDELIJA, INKA - Children'S Nutrition Research Center (CNRC)|
|STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)|
|Burrin, Douglas - Doug|
Submitted to: Amino Acids
Publication Type: Abstract Only
Publication Acceptance Date: 6/1/2013
Publication Date: 10/5/2013
Citation: Marini, J.C., Premkumar, M.H., Didelija, I.C., Stoll, B., Burrin, D.G. 2013. Arginine production in the neonate [abstract]. Amino Acids. 45:577.
Technical Abstract: Endogenous arginine synthesis in adults is a complex multiorgan process, in which citrulline is synthesized in the gut, enters the general circulation, and is converted into arginine in the kidney, by what is known as the intestinal-renal axis. In neonates, the enzymes required to convert citrulline into arginine are present in the intestines. Thus, the prevailing dogma is that this axis is not functional in neonates and that arginine, but not citrulline, is exported by the gut. Paradoxically, plasma citrulline is also used as a marker for gut health and development in the neonate. We have determined citrulline and arginine kinetics in piglets (6-10 days) using tracers. Whereas arginine flux increased during feeding (293 vs. 366 +/- 44 micromol/kg/h, P < 0.001), citrulline flux remained unchanged (74 +/- 7 micromol/kg/h, P = 0.432). The fractional contribution of citrulline to arginine synthesis remained constant (15.7 +/- 2.6%, P = 0.818), but the absolute amount increased during feeding (44 vs. 62 +/- 11 micromol/kg/h, P < 0.0001). Whereas 56 +/- 7% of the citrulline flux was accounted for as plasma arginine during fasting, a larger fraction (74 +/- 6% P < 0.0001) was accounted for during the feeding phase. The presence of argininosuccinate synthase and lyase in the gut was verified by immunohistochemistry. Although these two enzymes were present in the tip of the villi, the enzymes involved in citrulline synthesis were present in the crypts. Our results in neonatal pigs demonstrate a substantial citrulline flux that can be explained by the lack of colocalization of the enzymes for citrulline synthesis and further conversion into arginine.