Intestinal and hepatic metabolism of glutamine and citrulline in humans

Authors

  • Marcel C. G. Van De Poll,

    1. Department of Surgery, University Hospital Maastricht and Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands
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  • Gerdien C. Ligthart-Melis,

    1. Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands
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  • Petra G. Boelens,

    1. Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands
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  • Nicolaas E. P. Deutz,

    1. Department of Surgery, University Hospital Maastricht and Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands
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  • Paul A. M. Van Leeuwen,

    1. Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands
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  • Cornelis H. C. Dejong

    1. Department of Surgery, University Hospital Maastricht and Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands
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  • M. C. G. van de Poll and G. C. Ligthart-Melis contributed equally to this work. This paper has online supplemental material.

Corresponding author P. A. M. van Leeuwen: Department of surgery, VU University Medical Center, PO box 7057 1007 MB Amsterdam, the Netherlands.   Email pam.vleeuwen@vumc.nl

Abstract

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 inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The 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 were 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.

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