BIOSYNTHESIS OF NUCLEIC ACIDS 349 



When adenine-6-C^^ and N^^Ha were administered to E. coli,^'^ there was little (6%) 

 exchange of the amino group of the adenine incorporated, while 60% of the amino 

 group of the guanine was derived from the N^^Hs . This experiment also indicated no 

 lability of carbon 6. 



In this connection it might be noted that, in the catabolism'^-'^ of adenine-l,3-N2'^ 

 or" of uric acid-l,3-N2*' to uniformly labeled allantoin via the symmetrical inter- 

 mediate, hj'droxyacetylene diureide carboxylic acid, it is the 6-carbon which is lost. 

 There does not now appear to be any connection between the symmetrical distribu- 

 tion of the ureido moieties in the in vivo oxidation of uric acid and the equal labeling 

 of carbons 2 and 8 of purines by 1-carbon precursors. 



2, Precursors of Polynucleotide Pyrimidines 

 a. Pyrimidines 



The pattern of utilization of pyrimidines and pyrimidine derivatives 

 differs markedly from the general scheme of utiUzation of the purines and 

 their derivatives. Uracil, thymine/'* cytosine,*^ and the unnatural 2,6-di- 

 aminopyrimidine^^ were all found to be ineffective as nucleic acid precursors 

 in the rat. Later, a small incorporation of thymine- 1,3-N 2'^ into the poly- 

 nucleotide thymine of regenerating rat hver was detected, ^^ and a very 

 small incorporation of uracil-2-C^^ into rat PNA is reported.*^ The detection 

 of an incorporation of thymine in regenerating liver is reminiscent of the 

 far greater incorporation of adenine into regenerating as compared to nor- 

 mal Uver DNA. 



The only pyrimidine that can be readily utilized as a precursor of nucleic 

 acid in the rat is orotic acid (uracil-4-carboxylic acid). Although this com- 

 pound occurs naturally (Chapter 3), it is not a nucleic acid component and 

 yet all of the polynucleotide pyrimidines of the rat can be extensively de- 

 rived from orotic acid-1 ,3-N2^^" It has also been found that the polynucleo- 

 tide pyrimidines can be derived from orotic acid-2-C^^ in rat and human tis- 

 sues,^^'^' from orotic acid-4-C^'* in rats,^^ and from orotic acid-e-C'"* in rats®" 

 and in yeast. ^^-^^ All this evidence suggests that orotic acid is transformed 

 into polynucleotide pyrimidines without undergoing extensive degradation. 

 This question is discussed further in Chapter 23. 



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



" A. Bendich, W. D. Geren, and G. B. Brown, J. Biol. Chem. 185, 435 (1950). 



^* R. J. Rutman, A. Cantarow, K. E. Paschkiss, and B. Allanoff, Science 117, 282 



(1953). 

 " H. Arvidson, N. A. Eliasson, E. Hammarsten, P. Reichard, H. Ubisch, and S. 



Bergstrom, J. Biol. Chem. 179, 169 (1949). 

 58 L. L. Weed and D. W. Wilson, /. Biol. Chem. 189, 435 (1951). 

 " L. L. Weed, Cancer Research 11, 470 (1951). 

 60 R. B. Hurlbert and V. R. Potter, J. Biol. Chem. 195, 257 (1952). 

 " M. Edmonds, A. M. Delluva, and D. W. Wilson, J. Biol. Chem. 197, 251 (1952). 

 *2 The alternative numbering systems possible (cf . Chapter 3) may account for the 



references to both orotic acid-6 and 4-C*^ from this laboratory. 



