Route of administration (enteral or parenteral) affects the contribution of L-glutamine to de novo L-arginine synthesis in mice: a stable-isotope study

A pathway from enteral L-glutamine as substrate for L-arginine synthesis is suggested from previous studies. L-glutamine and L-glutamine dipeptides exhibit numerous beneficial effects in experimental and clinical studies. In trauma patients, enteral L-glutamine supply increased plasma L-arginine. The present study was designed to quantify the contribution of L-glutamine to the de novo L-citrulline and L-arginine synthesis in mice, when L-glutamine is administered in a high dose of labelled L-glutamine or L-alanyl-L-glutamine by the enteral or parenteral route. For this purpose, male Swiss mice (n=43) underwent a laparotomy and catheters were inserted for sampling and infusion. A primed, constant and continuous infusion of L-alanyl-L-[2,(15)N]glutamine (dipeptide groups) or L-[2,(15)N]glutamine (free L-glutamine groups), simultaneously with L-[ureido-(13)C-(2)H2]citrulline and L-[guanidino-(15)N2-(2)H2]arginine, was given (steady state model). Mice received the L-glutamine-tracers intravenously (jugular vein) or enterally (duodenum). Enrichments of metabolites were measured by liquid chromatography-mass spectrometry. Arterial L-glutamine concentrations were the highest in the intravenous dipeptide group. L glutamine was converted to L-citrulline and L-arginine when L-[2,(15)N]glutamine and L-alanyl-L-[2,(15)N]glutamine were given by enteral or parenteral route. The contribution of L-glutamine to the de novo synthesis of L-citrulline and L-arginine was higher in the enteral groups when compared with the intravenous groups (p<0.005). Therefore, the route of administration (enteral or parenteral) affects the contribution of L-glutamine, provided as free molecule or dipeptide, to the de novo synthesis of L-arginine in mice.