428 R. M. S. SMELLIE 



tent. Bendich et alP^ have observed that nearly 90% of administered 

 cytosine is eliminated in the urine of rats within 3 days, much of it in the 

 form of urea and ammonia. 



The pathway of pyrimidine breakdown in dogs proposed by Cerecedo^*^ '^^^ 

 envisages the conversion of uracil to isobarbituric acid, to isodialuric acid, 

 to formyloxaluric acid, to formic acid plus oxaluric acid, and finally to 

 oxalic acid plus urea. Thymine, on the other hand, is converted to thymine 

 glycol and finally yields carbon dioxide and urea. Recent studies on the 

 catabolism of pyrimidines by bacteria have been carried out by Hayaishi 

 and Kornberg,i9^'i95 ^ang and Lampen.i^e-iss and by Lara.i^^^o" The results 

 obtained by these workers with bacteria suggest that thymine glycol is 

 not an intermediate in the breakdown process, but that thymine is con- 

 verted to 5-methylbarbituric acid while uracil is oxidized to barbituric 

 acid (Fig. 6). The oxidation of the two substrates has been studied using 

 enzyme preparations from cell-free extracts, and it has been shown that 

 the same enzyme (uracil-thymine oxidase) is responsible for both reac- 

 tions.'^^ '^^^ Analysis of the products of reaction of this enzyme on thymine 

 and uracil have been carried out by Hayaishi and Kornberg,'^^ who have 

 found that the substances produced exhibit the ultraviolet spectra and 

 ion-exchange properties of 5-methylbarbituric acid and barbituric acid, 

 respectively. Lara'^^ has found that, in some instances, thymine may be 

 demethylated to uracil, but that this is not the normal pathway for the 

 oxidation of thymine. This pathway also appears to be that used in the 

 oxidation of the two aminopyrimidines, cytosine and 5-methylcytosine, 

 which are first deaminated by an adaptive enzyme to uracil and thymine, 

 respectively.'^^ These oxidation pathways are illustrated in the first part 

 of Fig. 6. 



The fate of the barbituric acid formed from uracil and cytosine has also 

 been studied using preparations of the enzyme (barbiturase) from cell-free 

 extracts of bacteria.'^^'^^ Barbituric acid is broken do^\^l to malonic acid 

 and urea, which is further hydrolyzed under the influence of urease to car- 

 bon dioxide and ammonia (Fig. 5). The further degradation of 5-methyl- 

 barbituric acid remains unknown ; it is readily destroyed by the intact cells 

 under aerobic conditions, but cell-free extracts exhibit no activity towards 

 this substrate. It seems not unlikely, however, that the 5-methylbarbituric 



>«3 A. Bendich, H. Getler, and G. B. Brown, /. Biol. Chem. 177, 565 (1949). 

 '" O. Hayaishi and A. Romberg, /. Am. Chem. Soc. 73, 2975 (1951). 

 1" O. Hayaishi and A. Romberg, /. Biol. Chem. 197, 717 (1952). 

 196 T. P. Wang, and J. O. Lampen, Federation Proc. 10, 267 (1951). 

 '" T. P. Wang and J. O. Lampen, /. Biol. Chem. 194, 775 (1952). 

 198 T. P. Wang and J. O. Lampen, /. Biol. Chem. 194, 785 (1952). 

 »'' F. J. S. Lara, /. Bacteriol. 64, 271 (1952). 

 ="'0 F. J. S. Lara, /. Bacteriol. 64, 279 (1952). 



