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

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...

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Published in:The American journal of clinical nutrition 2009-07, Vol.90 (1), p.95-105
Main Authors: Ligthart-Melis, Gerdien C, van de Poll, Marcel CG, Vermeulen, Mechteld AR, Boelens, Petra G, van den Tol, M. Petrousjka, van Schaik, Cors, De Bandt, Jean-Pascal, Deutz, Nicolaas EP, Dejong, Cornelis HC, van Leeuwen, Paul AM
Format: Article
Language:English
Subjects:
Amino acids
arginine
Arginine - biosynthesis
biochemical pathways
Biochemistry
Biological and medical sciences
biosynthesis
blood plasma
Body Mass Index
chemical reactions
citrulline
Citrulline - metabolism
Dipeptides - administration & dosage
Dipeptides - metabolism
Dipeptides - pharmacology
dose response
enteral feeding
Enteral Nutrition - methods
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
Gastrointestinal Diseases - surgery
glutamine
Glutamine - metabolism
hepatocytes
human nutrition
Humans
Infusions, Intravenous
intestines
intravenous injection
isotope labeling
Isotope Labeling - methods
Isotopes
kidney cells
liver
Male
metabolism
Middle Aged
Neoplasms - surgery
Nitrogen Isotopes
Patients
Peptides
quantitative analysis
stable isotopes
Surgery
temporal variation
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary: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.
ISSN:0002-9165
1938-3207
DOI:10.3945/ajcn.2008.26399