PYRIMIDINE NUCLEOSIDES AS PRECURSORS OF PYRIMIDINES IN POLYNUCLEOTIDES

Abstract

The purines and pyrimidines, so far the only known nitrogen-containing components of the polynucleotides, differ, with the exception of adenine, from most other nitrogenous substances, e.g.amino acids, in that when administered with the food they are not utilized by the rat.This was first shown by Plentl and Schoenheimer (l), who fed N15-labeled guanine, uracil, and thymine to rats and isolated the bases from the polynucleotides.They showed that in no case had isotope entered the purines or pyrimidines.The only substances containing the isotope in a significant amount were allantoin, after feeding guanine, and urea and ammonia after the pyrimidines were fed.These products were isolated from urine.The same negative results were obtained by Bendich, Getler, and Brown (2) with cytosine as the isotopic precursor.From these experiments the conclusion might be drawn that the pyrimidines present in food in the form of polynucleotides cannot act as precursors for the synthesis of new polynucleotides by the rat.This does not necessarily follow if, as is generally assumed, the digestive enzymes do not split off the free bases from dietary polynucleotides.Nucleosides formed by partial hydrolysis may be absorbed through the intestinal wall and these, unlike the free pyrimidines, might then be utilized for the synthesis of new polynucleotides by the animal.That a difference exists between free pyrimidines and pyrimidine nucleosides or nucleotides for certain organisms has been shown by Loring and Pierce (3) in experiments on mutants of Neurospora which require uracil for growth.Cytosine did not permit any growth.Both uridine and cytidine or the corresponding nucleotides could, however, be used instead of uracil.Furthermore the nucleosides and nucleotides allowed 10 to 60 times more growth than did an equimolar amount of uracil.The much higher activity of the nucleosides compared with that of the free bases may indicate a fundamental difference between the metabolism of free pyrimidine and pyrimidine bound to ribose.This difference may be valid for the rat also.