Myocardial Nucleotide Synthesis from Purine Bases and Nucleosides

Abstract

14 C-Labeled adenosine, inosine, hypoxanthine, and adenine were extracted by the isolated rat heart in amounts proportional to their concentration in the perfusion medium between 0.05 and 5 µM. With each of the precursor materials, nearly all of the radioactivity retained by the heart was identified as acid-soluble nucleotide. Nucleotide formation from the four isotopic precursors occurred at similar rates when the concentration of the precursors was below 1 µM. Above this concentration, the heart appeared to utilize adenosine for nucleotide synthesis at rates three to five times those for the other purines. Several experimental approaches were employed to determine the predominant enzymatic routes in the rat heart for the conversion of the nucleosides adenosine and inosine to nucleotides. The results indicated that adenosine was directly phosphorylated to 5'-adenosine monophosphate by a nucleoside kinase. Inosine appeared to proceed to the nucleotide, at least partially, through an initial conversion to hypoxanthine.