Oxygen tension does not affect urea synthesis in perifused rat hepatocytes

Perfusion of rat liver had led to the suggestion that oxygen tension, rather than the distribution of enzymes of urea synthesis, plays a key role in the regulation of urea synthesis in the periportal and pericentral areas of the liver lobule [F. W. Kari, H. Yoshihara and R. G. Thurman (1987) Eur. J. Biochem. 163, 1-7]. We have directly tested the effect of oxygen concentration on ureogenesis under steady-state conditions in isolated hepatocytes perifused with physiological concentrations of ammonia. We found that ureogenesis is independent of the oxygen concentration. Only at oxygen concentrations below 25 microM (which is below the oxygen concentration in liver) was urea synthesis decreased. This was because insufficient production of ATP led to decreased flux through carbamoyl-phosphate synthase. It is concluded that oxygen does not control urea synthesis.