Elevated plasma arginase-1 does not affect plasma arginine in patients undergoing liver resection.
Arginine is an important substrate in health and disease. It is a commonly held view that arginase-1 release from injured erythrocytes and hepatocytes leads to arginine breakdown; however, the true relationship between plasma arginase-1 concentration and activity has remained unaddressed. In the present study, blood was sampled from patients undergoing liver resection, a known cause of hepatocyte injury and arginase-1 release, to determine arginase-1, arginine and ornithine plasma levels. Arginase activity was assessed in vitro by measuring changes in arginine and ornithine plasma levels during incubation of plasma and whole-blood samples at 37 degrees C. Arginase-1 plasma levels increased 8-10-fold during liver resection, whereas arginine and ornithine levels remained unchanged. In accordance with these in vivo findings, arginine and ornithine levels remained unchanged in plasma incubated at 37 degrees C irrespective of the arginase-1 concentration. In contrast, arginine plasma levels in whole blood decreased significantly during incubation, with ornithine increasing stoichiometrically. These changes were irrespective of arginase-1 plasma levels and were explained by arginase activity present in intact erythrocytes. Next, plasma samples with 1000-fold normal arginase-1 concentrations were obtained from patients undergoing cadaveric liver transplantation. A significant decrease in arginine plasma levels occurred in vivo and in vitro. In contrast with commonly held views, moderately increased arginase-1 plasma levels do not affect plasma arginine. Very high plasma arginase-1 levels are required to induce potential clinically relevant effects.
van de Poll
Marcel C G
MC
Department of Surgery, University Hospital Maastricht & Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, 6200 Maastricht, The Netherlands. mcg.vandepoll@ah.unimaas.nl
Hanssen
Sebastiaan J P
SJ
Berbée
Maaike
M
Deutz
Nicolaas E P
NE
Monbaliu
Diethard
D
Buurman
Wim A
WA
Dejong
Cornelis H C
CH
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood; D001119:Arginase / Q000097:blood*; D001120:Arginine / Q000097:blood*; D001800:Blood Specimen Collection / Q000379:methods; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007432:Intraoperative Period; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009952:Ornithine / Q000097:blood; D011184:Postoperative Period
D000596:Amino Acids; D001120:Arginine; D009952:Ornithine; D001119:Arginase