Enteral administration of alanyl-[2-(15)N]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.


OBJECTIVE
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.


METHODS
The study was conducted under postabsorptive conditions during surgery. Sixteen patients received alanyl-[2-(15)N]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.
Ligthart-Melis
Gerdien C
GC
Department of Surgery, VU University Medical Center, Amsterdam, Netherlands.
van de Poll
Marcel C G
MC
Vermeulen
Mechteld A R
MA
Boelens
Petra G
PG
van den Tol
M Petrousjka
MP
van Schaik
Cors
C
De Bandt
Jean-Pascal
JP
Deutz
Nicolaas E P
NE
Dejong
Cornelis H C
CH
van Leeuwen
Paul A M
PA
D001120:Arginine / Q000096:biosynthesis*; D015992:Body Mass Index; D002956:Citrulline / Q000378:metabolism; D004151:Dipeptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004750:Enteral Nutrition / Q000379:methods*; D005260:Female; D005767:Gastrointestinal Diseases / Q000601:surgery; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000601:surgery; D009587:Nitrogen Isotopes
D004151:Dipeptides; D009587:Nitrogen Isotopes; D005973:Glutamine; D002956:Citrulline; D001120:Arginine; C054122:alanylglutamine