CONTROL OF RNA SYNTHESIS DURING LIVER REGENERATION - OMP PYROPHOSPHORYLASE AND DECARBOXYLASE ACTIVITIES IN NORMAL AND REGENERATING LIVER

The activities of orotidine 5′-phosphate (OMP) pyrophosphorylase (orotidine-5′-phosphate: pyrophosphate phosphoribosyl transferase) and OMP decarboxylase (orotidine-5′-phosphate carboxy-lyase) were determined in homogenates and cell fractions obtained from normal and regenerating rat liver. The conversion of orotic acid to UMP catalyzed by these two enzymes was determined by measuring the release of radioactive CO2 from [carboxy-14C]orotic acid. The overall reaction showed an absolute requirement for magnesium and pyrophosphorylribose 5′-phosphate. OMP pyrophosphorylase and decarboxylase activities of liver supernatant fraction change little during the first 12 h following partial hepatectomy. The peak of activity is reached at about 36 h after the operation. The increase in enzyme activity seems to be a reflection of OMP pyrophosphorylase activity. Homogenates from 18-h regenerating liver are 3 to 4 times more active than homogenates from normal livers in the conversion of orotic acid to UMP. Experiments using labeled adenine indicate that the availability of pyrophosphorylribose 5′-phosphate might be a limiting factor in normal liver homogenates. Microsomal fractions from normal livers have an inhibitory effect on the conversion acid to UMP by the supernatant fraction. Microsomal fractions obtained from the livers of partially hepatectomized animals have no effect. The pattern of increase of OMP pyrophosphorylase activity following partial hepatectomy suggests that the activity of this enzyme is not rate limiting for RNA synthesis at the early stages of liver regeneration. © 1969.