380 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



guide to those areas where there are great gaps in our knowledge. As the 

 acquisition of further basic information closes some of those gaps, it may be 

 possible, at some future date, to scrutinize, reinterpret, and integrate the 

 present information into a more satisfactory overall picture. 



1. Relation of Synthesis de novo to Incorporation of 

 Larger Precursors 



The developments in the area of the biosynthesis de novo of purine deriva- 

 tives have shown that the completion of the purine ring is accomplished 

 only after attachment of ribose and phosphate (Chapter 23). In all of those 

 studies inosinic acid has been found to be the first complete purine deriva- 

 tive formed,'^"'^^' and the gap from inosinic acid to "active" adenine or 

 guanine derivatives which can serve as precursors of the polynucleotide 

 purines remains unclosed. The possiblity also remains that the large pro- 

 duction of inosinic acid in the widely studied pigeon liver system, ^^^"^^^ 

 is a branch off the main pathway which is directed toward nitrogen dis- 

 posal, and that inosinic acid is not a member of the direct pathway leading 

 to the polynucleotide purines. 



The existence of mechanisms for the incorporation of exogenous adenine 

 into polynucleotide guanine and for the incorporation of exogenous guanine 

 into polynucleotide adenine are each demonstrated in various species. In 

 most instances both mechanisms clearly exist, but the conversion in one 

 or the other direction predominates (Fig. 2). Even in the rat, where the 

 conversion of adenine or adenine derivatives into polynucleotide guanine is 

 strongly favored, polynucleotide guanine can arise by pathways other than 

 via adenine derivatives, as shown by the fact that in some instances there 

 is a greater incorporation of small precursors into the guanine than into 

 the adenine."' It seems plausible that there is a common metabolic path- 

 way for the assembly of the purine nucleotide skeleton, and that this 

 branches into two pathways leading, respectively, to adenine and guanine 

 derivatives. These general relationships can be schematically depicted as in 

 Fig. 5. 



a. The Directness of the Incorporation of Exogenous Adenine 



When exogenous adenine or guanine is available, each appears to be in- 

 corporated quite directly into "active" derivatives which represent later 

 stages in the respective pathways leading to the polynucleotide purines. 



160 J. M. Buchanan and D. W. Wilson, Federation Proc. 12, 646 (1953). 



1" G. R. Greenberg, Federation Proc. 12, 651 (195.3). 



lea W. Schuler and W. Reindel, Z. physiol. Chem. 221, 209, 232 (19.33). 



163 N. L. Edson, H. A. Krebs, and A. Model, Biochem. J. 30, 1380 (1936). 



'64 A. Orstrom, M. Orstrom, and H. A. Krebs, Biochem. J. 33, 990 (1939). 



166 G. R. Greenberg, J. Biol. Chem. 190, 611 (1951). 



i6» M, P. Schulman, J. C. Sonne, and J. M. Buchanan, J. Biol. Chem. 196, 499 (1952). 



