344 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



(NIB) ^as used" to show that ammonia is a precursor of the nitrogen of the 

 nucleic acid purines and pyrimidines in the rat and the pigeon. Other 

 investigations involving the use of labeled compounds have demonstrated 

 that many simple substances can be utilized in the biosynthesis of various 

 polynucleotide components (Chapters 22, 23), and extensive use has been 

 made of the incorporation of such smaller precursors into polynucleotides 

 in the course of studies directed at the nucleic acids themselves. 



1. Precursors of the Polynucleotide Purines 



The demonstration of the participation of simple substances in the bio- 

 synthesis of purines and pyrimidines, and the failure to find a nutritional 

 requirement for any nucleic acid derivative (other than phosphate) for most 

 living forms, cannot be interpreted to mean that purines, pyrimidines, nu- 

 cleosides, or nucleotides are not involved in the biosynthesis of nucleic 

 acids. Indeed, it does not seem likely that during the process of cellular 

 biosynthesis of the nucleic acids all of the simple precursors are simul- 

 taneously assembled and "snapped together" into a complex polynucleotide. 

 Rather, it would seem that simple precursors would be built into complex 

 compounds and these then constructed into more complex substances until 

 finally the polynucleotide is formed. On the assumption that this is the 

 pattern of nucleic acid biosynthesis, a considerable amount of work has 

 been done to determine the possible nature of the intermediates involved in 

 such a scheme. The search for these intermediates has centered chiefly upon 

 the hydrolysis products of nucleic acid, not only because such compounds 

 might reasonably be expected to be precursors, but also because they could 

 be made available as labeled compounds either by organic synthesis, bio- 

 synthesis, or by enzymic synthesis. 



a. Adenine and Derivatives 



The first demonstration of the participation of a nucleic acid constituent 

 in a process of biosynthesis was the finding^^-^' that, in the rat, dietary 

 adenine is incorporated into tissue nucleic acids as adenine and that it is 

 also a precursor of nucleic acid guanine. When adenine-1 ,3-N2^^ was fed at 

 a level of 0.2 mM. per kilogram of body weight per day for 3 days, 5.4 % of 

 the adenine and 3.2 % of the guanine of the mixed nucleic acids of the viscera 

 were derived from the dietary compound, and these values were increased 

 to 13.7 and 8.2 %, respectively, when the level of administration was in- 

 creased to 1.5 mM. per kilogram of body weight per day. These values 

 represent incorporations into mixed PNA and DNA of rat viscera, but, in 



11 F. W. Barnes, Jr., and R. Schoenheimer, J. Biol. Chem. 151, 123 (1943). 

 >2 G. B. Brown, P. M. Roll, and A. A. Plentl, Federation Proc. 6, 517 (1947). 

 '3 G. B. Brown, P. M. Roll, A. A. Plentl, and L. F. Cavalieri, J. Biol. Chem. 172, 469 

 (1948). 



