Possible Rate-Limiting Factors in Urea Synthesis by the Perfused Rat Liver 1

Abstract

Summary

Rates of urea synthesis from ammonium chloride by perfused rat livers, pretreated with different diets and hormones, were measured. Addition of ornithine to the perfusion media increased rates of urea synthesis, but not in proportion to the relative amount of argininosuccinate synthetase activity present. Livers from rats receiving a protein-free diet for 4 days were reported to have about 12% of the argininosuccinate synthetase (E.C. 6.3.4.5.) activity as livers from rats receiving a high-protein diet or rats pretreated with cortisol. However, in the presence of excess ornithine all 3 groups of rats synthesized urea at the same rate.

This investigation suggests that under conditions in which high ammonia concentrations prevailed a factor or factors in addition to urea-cycle intermediates and the activity of urea-cycle enzymes were limiting the rate of urea synthesis, and that there was not a correlation between maximum rate of urea synthesis and the activity of argininosuccinate synthetase.

The authors wish to thank Mr. E. Avery for his technical assistance.