Metabolism of cytosine, thymine, uracil, and barbituric acid by bacterial enzymes.

Early stud& with pyrimidines administered t.o animals established the fact that, these compounds arc metabolized (3, 4). Present concepts of the pathways of pyrimidine metabolism stem largely from the work of Cerecedo (4), in which he measured the changes in the urinary excretion of urea after feeding pyrimidines and related subst.ances. On the basis of these studies, he proposed an init.ial oxidation at carbon 5, which in the case of uracil yields isobarbituric acid and with t.hymine results in thymine glycol. It was furt.her proposed that oxalic acid, formic acid, and urea are ult.imately obtained from uracil and t,hat acetol, carbon dioxide, and urea result from thymine. However, the indirect nature of the evidence leaves this scheme open t’o question. Our approach to this problem has been first to obtain, through enrichment culture, bact.erial strains which rapidly metabolize pyrimidines and then to investigate the detailed metabolic pathway with enzymes obtained from these bacteria. Results both with whole cells and partially purified enzymes have suggested the pathway of pyrimidine metabolism indicated in Fig. 1.