title: Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Surgery, Nutrition and Toxicology Institute Maastricht, Maastricht University and University Hospital Maastricht, Netherlands. mcg.vandepoll@ah.unimaas.nl
authors.forename: Marcel C G
authors.initials: MC
authors.lastname: van de Poll
authors.forename: Michiel P C
authors.initials: MP
authors.lastname: Siroen
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: Peter B
authors.initials: PB
authors.lastname: Soeters
authors.forename: Gerdien C
authors.initials: GC
authors.lastname: Melis
authors.forename: Petra G
authors.initials: PG
authors.lastname: Boelens
authors.forename: Nicolaas E P
authors.initials: NE
authors.lastname: Deutz
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000378:metabolism*; D001783:Blood Flow Velocity; D002956:Citrulline / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000601:surgery; D005260:Female; D005973:Glutamine / Q000378:metabolism; D006498:Hepatectomy; D006801:Humans; D007421:Intestine, Small / Q000098:blood supply / Q000378:metabolism* / Q000601:surgery; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D009952:Ornithine / Q000378:metabolism
chemical_list: D005973:Glutamine; D002956:Citrulline; D001120:Arginine; D009952:Ornithine