Pyrimidine nucleotide synthesis in the normal and hypertrophying rat heart. Relative importance of the de novo and "salvage" pathways.

Abstract

Radioactive orotic acid incorporation into RNA (de novo pathway of pyrimidine nucleotide synthesis) was considerably lower for rat heart than for rat liver in vivo and in vitro. 3 H uridine ("salvage" pathway) was incorporated into heart RNA to a greater extent than 3 H orotic acid, and the labeling with uridine in the heart exceeded that in the liver. Extracts of heart showed little enzymatic conversion of orotic acid to pyrimidine nucleotides in the presence of ATP and ribose-5-phosphate, a condition under which there was good activity in other tissues such as the liver, spleen, and kidney. Addition of phosphoribosylpyrophosphate (PRPP) markedly enhanced orotic acid conversion though it still remained less for heart than for other tissues. These findings indicated that PRPP synthetase activity was low in the heart. Uridine kinase activity in the heart was similar to that in the liver. Uridine kinase appeared to be rate limiting in the "salvage" pathway. Aortic constriction produced an increase in uridine kinase activity at 24 hours with a peak at 2 to 6 days (50 to 60% stimulation) after operation, while uridylate kinase, uridine phosphorylase, and orotidine monophosphate pyrophosphorylase activities remained unchanged. The "salvage" pathway appears to play an important role in pyrimidine nucleotide synthesis in the heart, and uridine kinase may be regulatory in this pathway during cardiac hypertrophy.