328 GEORGE W. CROSBIE 



dione (4-azauracil) with respect to a number of species of microorganisms 

 is due to an inhibition of orotidine-5'-phosphate decarboxylase. The orotic 

 acid analogs, uracil-4-sulfonic acid, uracil-4-sulfonamide, and uracil-4- 

 methylsulfone, inhibit the growth of certain orotic acid-requiring strains 

 of Lactobacillus bulgaricus. These analogs have been shown recently to in- 

 hibit competitively the conversion of orotic acid to orotidine-S'-phosphate 

 by a partially purified orotidine-5'-phosphate pyrophosphorylase of yeast. 35a 

 No action on orotidine-5'-phosphate decarboxylase could be detected (see 

 Chapter 39). 



Yates and Pardee 3515 have demonstrated a control of pyrimidine nucleotide 

 synthesis in E. coli by feed-back inhibition. They have shown that cytidine 

 and especially cytidine-5'-phosphate are competitive inhibitors with aspar- 

 tic acid and carbamyl phosphate for carbamylaspartic acid formation. 

 Uracil, uridine, uridine-5'-phosphate, and cytosine do not inhibit appre- 

 ciably. 



c. Biosynthesis from Preformed Pyrimidines 



The ability of tissues to incorporate uracil, uridine, and uridine-2'-, 3'-, 

 and 5'-phosphates into polynucleotides has been the subject of some in- 

 vestigation. 36 ' 38 Plentl and Schoenheimer 39 and Rutman et a/. 40 have clearly 

 indicated the inability of rat liver to utilize uracil for ribonucleic acid syn- 

 thesis. Cytosine is similarly not utilized. 41 On the other hand, pyrimidine 

 nucleosides and nucleotides do function as precursors of tissue polynucleo- 

 tide pyrimidines. 38 ' 4244 It must be noted, however, that no evidence for 

 the utilization of intact pyrimidine ribonucleotides has been presented. 

 Liebman and Heidelberger 46 have shown that the extent of incorporation of 

 P 32 -labeled pyrimidine-2'-, 3'-, and 5'-ribonucleotides into the polynucleo- 

 tides of Ehrlich ascites carcinoma cells, rat liver slices, and the Flexner- 



38a W. L. Holmes, J. Biol. Chem. 223, 677 (1956). 



35b R. A. Yates and A. B. Pardee, J. Biol. Chem. 221, 757 (1956). 



36 E. Hammarsten and P. Reichard, J. Biol. Chem. 183, 105 (1950). 



36a U. Lagerkvist, P. Reichard, B. Carlsson, and G. B. Grabosz, Cancer Research 15, 



164 (1955). 

 « F. J. Di Carlo, A. S. Schultz, P. M. Roll, and G. B. Brown, J. Biol. Chem. 180, 

 329 (1949). 



38 P. M. Roll, G. B. Brown, F. J. Di Carlo, and A. S. Schultz, J. Biol. Chem. 180, 

 333 (1949). 



39 A. A. Plentl and R. Schoenheimer, J. Biol. Chem. 153, 203 (1944). 



40 R. J. Rutman, A. Cantarow, and K. E. Paschkis, Cancer Research 14, 119 (1954). 



41 A. Bendich, H. Getler, and G. B. Brown, J. Biol. Chem. 177, 565 (1949). 



42 E. Hammarsten, P. Reichard, and E. Saluste, Acta Chem. Scand. 3, 433 (1949). 



43 W. H. Prusoff, J. Biol. Chem. 231, 873 (1958). 



44 L. I. Hecht and V. R. Potter, Cancer Research 16, 999 (1956). 



45 K. C. Liebman and C. Heidelberger, J. Biol. Chem. 216, 823 (1955). 



