Synthesis of pyrimidine nucleotides in rat myocardium: potential role of blood cytidine.

Plasma contains micromolar concentrations of pyrimidine bases and nucleosides: uracil 1.9 +/- 0.1 (n = 29), cytosine 1.1 +/- 0.01 (n = 29), uridine 1.2 +/- 0.1 (n = 56) and cytidine 5.4 +/- 0.1 (n = 59) (means +/- S.E.M.). Accordingly, we postulated that these compounds could be used as the main precursors for myocardial pyrimidine nucleotide synthesis. The kinetics of the incorporation of blood plasma bases and nucleosides into myocardial nucleotides was studied by in vivo radio-isotopic studies in rats. The clearance of the radiolabelled compounds in blood plasma and the incorporation of radiolabelled precursors into liver nucleotides was also investigated. The results can be summarized as follows: (1) The pyrimidine radioactive bases were only very slightly incorporated into heart nucleotides 1 h after injection: thus 1 h after injection any incorporation of radiolabelled cytosine into nucleotides remained undetectable and for radioactive uracil the ratio of the specific radioactivity of uracil nucleotides to that of plasma uracil remained below 0.7%. (2) Radiolabelled plasma uridine was subject to a far more rapid catabolism than radiolabelled plasma cytidine. (3) The labelling of myocardial uracil nucleotides from plasma uridine was very slight. Their specific radioactivity represented less than 16% of plasma uridine specific radioactivity. (4) When the tracer was cytidine the specific radioactivity of cytosine nucleotides reached that of precursor within 30 min after injection and uracil nucleotides were also labeled (10% of cytidine nucleotides specific radioactivity). These results, and other previous data, suggest the possibility that the pyrimidine nucleotide synthesis in the rat heart may be largely achieved via the phosphorylation of blood plasma cytidine.