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 by 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 labeled 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-[2-15N]glutamine (dipeptide groups) or l-[2-15N]glutamine (free l-glutamine groups), simultaneously with l-[ureido-13C,2H2]citrulline and l-[guanidino-15N2,2H2]arginine, was given (steady-state model). Mice received the l-glutamine tracers intravenously (jugular vein) or enterally (duodenum). Enrichments of metabolites were measured by LC-MS. Arterial l-glutamine concentrations were the highest in the intravenous dipeptide group. l-Glutamine was converted to l-citrulline and l-arginine when l-[2-15N]glutamine and l-alanyl-l-[2-15N]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.