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Removal of Glycylglutamine from Plasma by Individual Tissues: Mechanism and Impact on Amino Acid Fluxes in Postabsorption and Starvation^{1 ,2}

Siamak A. Adibi^*,3, Herbert Lochs, Naji N. Abumrad, Hannelore Daniel and Jorge A. Vazquez^*

^* Clinical Nutrition Research Unit, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 1st Medical University Clinic, University of Vienna, Vienna, Austria Department of Surgery, State University of New York at Stony Brook, Stony Brook, NY Institute of Nutrition, University of Giessen, Giessen, Germany

A possible source of glutamine, for inclusion in the parenteral solutions, is glycylglutamine. The aim of this article is to review briefly the information on metabolism of glycylglutamine when administered intravenously. The fact that there is efficient utilization of intravenously infused glycylglutamine was evident with very little excretion in the urine. Although all the tissues examined, except brain, participated in the removal of glycylglutamine from plasma, kidney predominated in this regard. This may be related to the presence of carrier-mediated systems for cellular uptake of glycylglutamine in the kidney and the lack of them in other tissues. Starvation did not alter the metabolic clearance of glycylglutamine, although it reduced the removal by the kidney. Renal metabolism of glycylglutamine resulted in the release of constituent amino acids that were largely utilized by the liver in the postabsorptive state and by skeletal muscle in starvation. This alteration was accompanied by a selective inhibition of muscle release of amino acids that are substrates for enhanced hepatic gluconeogenesis and renal ammoniagenesis in starvation. Because there was no change either in plasma glucose level or ammonia excretion during the infusion of glycylglutamine in starved human subjects, apparently the amino acid residues of glycylglutamine fulfilled the substrate needs for these functions. These results provide a metabolic basis for further investigations of the possible nutritional benefit of including glycylglutamine in parenteral nutrition.

KEY WORDS: • glycylglutamine • human • glutamine • amino acid fluxes • starvation

¹ Presented as part of the 33rd Annual Ruminant Nutrition Conference: Nutritional and Hormonal Regulation of Amino Acid Metabolism, given at the 76th Annual Meeting of the Federation of American Societies for Experimental Biology, Anaheim, CA, April 5, 1992. This conference was sponsored by the American Institute of Nutrition and was supported by grants from Merck & Co., Inc.; SmithKline Beecham Animal Health; Monsanto Agricultural Company; The Upjohn Company; Farmland Industries, Inc.; Purina Mills, Inc.; Syntex Research; Cargill, Nutrena Feed Division; NutriBasics Company and Carolina By-Products Company. Guest editor for this symposium was Joan H. Eisemann, Department of Animal Science, North Carolina State University, Raleigh, NC 27695.

² Supported by National Institutes of Health grant DK-15861.

³ To whom correspondence should be addressed: Clinical Nutrition Research Unit, Montefiore University Hospital, 3459 Fifth Avenue, Pittsburgh, PA 15213.

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