Journal
AMERICAN JOURNAL OF CLINICAL NUTRITION
Volume 85, Issue 1, Pages 167-172Publisher
AMER SOC NUTRITION-ASN
DOI: 10.1093/ajcn/85.1.167
Keywords
glutamine; citrulline; arginine; gut; liver; kidney; interorgan amino acid exchange; humans
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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 convened 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.
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