Background: Glutamine exhibits numerous beneficial effects in
experimental and clinical studies. It has been suggested that these effects
may be partly mediated by the conversion of glutamine into citrulline and
arginine. The intestinal metabolism of glutamine appears to be crucial in this
pathway. The present study was designed to establish the effect of the feeding
route, enteral or parenteral, on the conversion of exogenously administered
glutamine into citrulline and arginine at an organ level in humans, with a
focus on gut metabolism. Methods: Sixteen patients undergoing upper
gastrointestinal surgery received an IV or enteral (EN) infusion of
l-[2-15N]glutamine. Blood was sampled from a radial
artery and from the portal and right renal vein. Amino acid concentrations and
enrichments were measured, and net fluxes of [15N]-labeled
substrates across the portal drained viscera (PDV) and kidneys were calculated
from arteriovenous differences and plasma flow. Results: Arterial
[15N]glutamine enrichments were significantly lower during enteral
tracer infusion (tracer-to-tracee ratio [labeled vs unlabeled
substrate, TTR%] IV: 6.66 ± 0.35 vs EN: 3.04 ± 0.45;
p < .01), reflecting first-pass intestinal metabolism of glutamine
during absorption. Compared with IV administration, enteral administration of
the glutamine tracer resulted in a significantly higher intestinal fractional
extraction of [15N]glutamine (IV: 0.15 ± 0.03 vs
EN: 0.44 ± 0.08 μmol/kg/h; p < .01). Furthermore,
enteral administration of the glutamine tracer resulted in higher arterial
enrichments of [15N]citrulline (TTR% IV: 5.52 ± 0.44
vs EN: 8.81 ± 1.1; p = .02), and both routes of
administration generated a significant enrichment of [15N]arginine
(TTR% IV: 1.43 ± 0.12 vs EN: 1.68 ± 0.18). This was
accompanied by intestinal release of [15N]citrulline across the
PDV, which was higher with enteral glutamine (IV: 0.38 ± 0.07
vs EN: 0.72 ± 0.11 μmol/kg/h; p = .02), and
subsequent [15N]arginine release in both groups.
Conclusions: In humans, the gut preferably takes up enterally
administered glutamine compared with intravenously provided glutamine. The
route of administration, enteral or IV, affects the quantitative conversion of
glutamine into citrulline and subsequent renal arginine synthesis in
humans.
The present study in humans shows that the gut preferably takes up enterally administered glutamine compared to intravenously provided glutamine. Enteral glutamine is subsequently more avidly metabolized into citrulline, which was observed to be the precursor of arginine.
