Intestinal renal metabolism of L-citrulline and L-arginine following enteral or parenteral infusion of L-alanyl-L-[2,N]glutamine or L-[2,N]glutamine in mice

Boelens, Petra G., Paul A. M. van Leeuwen, Cornelis H. C. Dejong, and Nicolaas E. P. Deutz. Intestinal renal metabolism of L-citrulline and L-arginine following enteral or parenteral infusion of L-alanyl-L-[2,N]glutamine or L-[2,N]glutamine in mice. Am J Physiol Gastrointest Liver Physiol 289: G679–G685, 2005. First published July 28, 2005; doi:10.1152/ajpgi.00026.2005.—Previously, we observed increased plasma arginine (ARG) concentrations after glutamine (GLN)-enriched diets, in combination with clinical benefits. GLN delivers nitrogen for ARG synthesis, and the present study was designed to quantify the interorgan relationship of exogenous L-GLN or GLN dipeptide, by enteral or parenteral route, contributing to intestinal citrulline (CIT) and renal de novo ARG synthesis in mice. To study this, we used a multicatheterized mouse model with Swiss mice (n 43) in the postabsorptive state. Stable isotopes were infused into the jugular vein or into the duodenum {per group either free L-[2,N]GLN or dipeptide L-ALA-L-[2,N]GLN, all with L-[ureidoC-H2]CIT and L-[guanidino-N2-H2]ARG} to establish renal and intestinal ARG and CIT metabolism. Blood flow was measured using C-para-aminohippuric acid. Net intestinal CIT release, renal uptake of CIT, and net renal ARG efflux was found, as assessed by arteriovenous flux measurements. Quantitatively, more de novo L-[2,N]CIT was produced when free L-[2,N]GLN was given than when L-ALA-L-[2,N]GLN was given, whereas renal de novo L-[2,N]ARG was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice in that L-[2,N]GLN or dipeptide were both converted into de novo renal L-[2,N]ARG; however, not all was derived from intestinal L-[2,N]CIT production. In this model, the feeding route and form of GLN did not influence de novo renal ARG production derived from GLN.