TY - JOUR
T1 - Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism
AU - van de Poll, M.C.
AU - Siroen, M.P.
AU - van Leeuwen, P.A.
AU - Soeters, P.B.
AU - Melis, G.C.
AU - Boelens, P.G.
AU - Deutz, N.E.
AU - Dejong, C.H.
PY - 2007/1/1
Y1 - 2007/1/1
N2 - 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.
AB - 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.
U2 - 10.1093/ajcn/85.1.167
DO - 10.1093/ajcn/85.1.167
M3 - Article
SN - 0002-9165
VL - 85
SP - 167
EP - 172
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 1
ER -