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This Article Full Text Full Text (PDF) All Versions of this Article: 90/1/95    most recent ajcn.2008.26399v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ligthart-Melis, G. C Articles by van Leeuwen, P. A. PubMed PubMed Citation Articles by Ligthart-Melis, G. C Articles by van Leeuwen, P. A. Agricola Articles by Ligthart-Melis, G. C Articles by van Leeuwen, P. A.

Enteral administration of alanyl-[2-¹⁵N]glutamine contributes more to the de novo synthesis of arginine than does intravenous infusion of the dipeptide in humans^1,2,3,4,5

¹ From the Department of Surgery, VU University Medical Center, Amsterdam, Netherlands (GCL-M, MARV, PGB, MPvdT, CvS, and PAMvL); the Department. of Surgery, University Hospital Maastricht & Nutrition and Toxicology Research Institute Maastricht, Maastricht, Netherlands (MCGvdP, NEPD, and CHCD); and Clinical Biochemistry, Université Paris Descartes, Paris, France (J-PDB).

² GCL-M and MCGvdP contributed equally to this work and share first authorship.

³ Supported by a grant from the Netherlands Organization for Health Research and Development to PGB (920-03-185 AGIKO) and by a grant from Fresenius-Kabi, Bad Homburg, Germany.

⁴ Present address for NEPD: Center for Translational Research on Aging & Longevity, Donald W Reynolds Institute of Aging, University of Arkansas for Medical Sciences, Little Rock, AR.

⁵ Address correspondence to PAM van Leeuwen, Department of Surgery, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, Netherlands. E-mail: pam.vleeuwen{at}vumc.nl.

Background: We previously confirmed in humans the existence of a pathway of glutamine into citrulline and arginine, which is preferentially stimulated by luminally provided glutamine. However, because glutamine is unstable, we tested this pathway with a stable dipeptide of glutamine.

Objectives: The objectives were to explore whether alanyl-glutamine contributes to the synthesis of arginine in humans and whether this depends on the route of administration.

Design: The study was conducted under postabsorptive conditions during surgery. Sixteen patients received alanyl-[2-¹⁵N]glutamine enterally or intravenously together with intravenously administered stable-isotope tracers of citrulline and arginine. Blood was collected from an artery, the portal vein, a hepatic vein, and the right renal vein. Arterial and venous enrichments and (tracer) net balances of alanyl-glutamine and glutamine, citrulline, and arginine across the portal-drained viscera, liver, and kidneys were determined. Parametric tests were used to test results (mean ± SEM). P < 0.05 was considered significant.

Results: Twice as much exogenous glutamine was used for the synthesis of citrulline when alanyl-glutamine was provided enterally (5.9 ± 0.6%) than when provided intravenously (2.8 ± 0.3%) (P < 0.01). Consequently, twice as much exogenous glutamine was used for the synthesis of arginine when alanyl-glutamine was provided enterally (5 ± 0.7%) than when provided intravenously (2.4 ± 0.2%) (P < 0.01). However, results at the organ level did not explain the differences due to route of administration.

Conclusions: Alanyl-glutamine contributes to the de novo synthesis of arginine, especially when provided enterally. A stable-isotope study using a therapeutic dose of alanyl-glutamine is needed to investigate the clinical implications of this finding.