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First published online on March 8, 2007.
 Copyright © 2007 by The Physiological Society
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jphysiol.2006.126029v1
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Received December 13, 2006
Revised January 11, 2007
Accepted after revision March 5, 2007

Intestinal and hepatic metabolism of glutamine and citrulline in humans

Marcel CG van de Poll1, Gerdien C Ligthart-Melis2, Petra G Boelens2, Nicolaas EP Deutz1, Paul AM van Leeuwen2*, and Cornelis HC Dejong1

1 University Hospital Maastricht, Department of Surgery; Maastricht University, NUTRIM
2 VU University Medical Center, Department of Surgery

* To whom correspondence should be addressed. E-mail: pam.vleeuwen{at}vumc.nl.

Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving interorgan transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans however, has remained unaddressed. Aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-15N] glutamine and [ureido-13C-2H2] citrulline. Arterial, portal venous and hepatic venous blood was sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans.


Key words: Amino acid metabolism • Arginine • Glutamine




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