TY - JOUR
T1 - Intestinal and hepatic metabolism of glutamine and citrulline in humans
AU - van de Poll, M.C.
AU - Ligthart Melis, G.C.
AU - Boelens, P.G.
AU - Deutz, N.E.
AU - van Leeuwen, P.A.
AU - Dejong, C.H.
PY - 2007/1/1
Y1 - 2007/1/1
N2 - 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.
AB - 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.
U2 - 10.1113/jphysiol.2006.126029
DO - 10.1113/jphysiol.2006.126029
M3 - Article
C2 - 17347276
SN - 0022-3751
VL - 581
SP - 819
EP - 827
JO - Journal of Physiology
JF - Journal of Physiology
IS - Pt2
ER -