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Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism^1,2,3

¹ From the Department of Surgery, Nutrition and Toxicology Institute Maastricht, Maastricht University and University Hospital Maastricht, Netherlands (MCGvdP, PBS, NEPD, and CHCD), and the Department of Surgery, VU University Medical Center, Amsterdam, Netherlands (MPCS, PAMvL, GCM, and PGB)

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.

Key Words: Glutamine • citrulline • arginine • gut • liver • kidney • interorgan amino acid exchange • humans

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