Uptake and Metabolism of Plasma Glutamine by the Small Intestine

Abstract An isolated, vascularly perfused preparation of rat intestine extracted large amounts of glutamine (75 µmoles per hour), but no other amino acid, from a recirculated blood perfusate. With l-U-14Cglutamine, the carbon was partly incorporated into tissue acid-insoluble material (14%) and the rest reappeared with little delay in intestinal venous blood in CO2 (57%), citrulline (6%), proline (5%), and organic acids (18%), predominantly citric acid and lactic acid. Perfusate glutamine was the source of 32% of the CO2 produced by the preparation, although the perfusate contained 10 to 15 mm glucose. Most glutamine uptake and metabolism occurred in the small intestinal mucosal cells and, from analyses of labeled tissue metabolites, appeared to proceed via glutamic acid. The rapid flow of glutamine carbon through mucosa may be explained in part by the small glutamine pool, only 0.2 µmole per g of tissue. Glutamine nitrogen taken up by intestine could be approximately accounted for by the quantities of citrulline (34%), alanine (33%), ammonia (23%), and proline (10%) released back into the perfusate. Glutamine uptake comparable to that found in the isolated organ was observed in vivo, from arteriovenous concentration measurements across intestine in fasted dogs, cats, hamsters, monkeys, and conventional and germ-free rats. Twenty-five to 33% of plasma glutamine was extracted in each pass through the tissue. Glutamine uptake persisted in rats during transport of large amounts of glutamic acid from the intestinal lumen into the blood and in rats injected with 6-diazo-5-oxo-l-norleucine. The results of these studies suggest that glutamine derived from blood is an important respiratory substrate for cells in the small intestinal mucosa and that intestine is a major site for metabolism of glutamine released into the circulation by other tissues.