Pyrimidine nucleotide synthesis in rat liver after the administration of cycloheximide.

After the administration of cycloheximide (2 mg/kg) the utilization of [2(-14C)]orotic acid for the synthesis of pyrimidine nucleotides of acid-soluble extracts of the liver is not affected for about 7 h. The specific activities of uridine and cytidine components are increased later on, and this increase is higher in the case of cytidine components. Analogous changes undergoes the specific activity of RNA pyrimidine nucleotides. The increased utilization of labeled orotic acid for the synthesis of cytidine nucleotides can be observed also in the kidney and in the small intestine. The enhanced degree of labeling of cytidine nucleotides in vivo cannot be correlated with the activity of cytidine triphosphate synthetase (EC 6.3.4.2) of liver cytosol estimated in vitro. The amination of UTP is suppressed at later intervals after the application of cycloheximide. The same holds true for the activity of uridine phosphorylase (EC 2.4.2.3),5'-nucleotidase (EC 3.1.3.5) ATPase (EC 3.6.1.3) and of liver cytosol. The activity of uridine kinase (EC 2.7.1.48) is increased when tested both with uridine and cytidine as substrates. Cytidine deaminase activity (EC 3.5.4.5) raises markedly 3--5 h after the administration of drug; later on it decreases again.