Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism

Am J Clin Nutr. 2007 Jan;85(1):167-72. doi: 10.1093/ajcn/85.1.167.


Background: The liver plays a central role in amino acid metabolism. However, because of limited accessibility of the portal vein, human data on this subject are scarce.

Objective: We studied hepatic amino acid metabolism in noncirrhotic fasting patients undergoing liver surgery.

Design: Twenty patients undergoing hepatectomy for colorectal metastases in a normal liver were studied. Before resection, blood was sampled from a radial artery, portal vein, hepatic vein, and renal vein. Organ blood flow was measured by duplex ultrasound scan.

Results: The intestine consumed glutamine and released citrulline. Citrulline was taken up by the kidney. This was accompanied by renal arginine release, which supports the view that glutamine is a precursor for arginine synthesis through an intestinal-renal pathway. The liver was found to extract citrulline from this pathway at a rate that was dependent on intestinal citrulline release (P < 0.0001) and hepatic citrulline influx (P = 0.03). Fractional hepatic extractions of citrulline (8.4%) and arginine (11.5%) were not significantly different. Eighty-eight percent of arginine reaching the liver passed it unchanged. Splanchnic citrulline release could account for one-third of renal citrulline uptake.

Conclusions: This is the first study of hepatic and interorgan amino acid metabolism in humans with a normal liver. The data indicate that glutamine is a precursor of ornithine, which can be converted to citrulline by the intestine; citrulline is transformed in the kidneys to arginine. Hepatic citrulline uptake limits the amount of gut-derived citrulline reaching the kidney. These findings may have implications for interventions aimed at increasing systemic arginine concentrations.

MeSH terms

  • Adult
  • Aged
  • Arginine / metabolism*
  • Blood Flow Velocity
  • Citrulline / metabolism*
  • Colorectal Neoplasms / surgery
  • Female
  • Glutamine / metabolism
  • Hepatectomy
  • Humans
  • Intestine, Small / blood supply
  • Intestine, Small / metabolism*
  • Intestine, Small / surgery
  • Kidney / blood supply
  • Kidney / metabolism*
  • Liver / blood supply
  • Liver / metabolism*
  • Liver / surgery
  • Male
  • Middle Aged
  • Organ Specificity
  • Ornithine / metabolism


  • Glutamine
  • Citrulline
  • Arginine
  • Ornithine