BIOSYNTHESIS OF PURINES AND PYRIMIDINES 293 



leads to the formation of excretory uric acid, must necessarily be involved 

 at all in the synthesis of polynucleotide purines. All comparisons between 

 the small molecule precursors for uric acid and those for polynucleotide 

 purines have, however, shown no differences. Furthermore, the demon- 

 stration of the synthesis of inosinic acid in yeast extracts by Williams and 

 Buchanan^" shows that this nucleotide is synthesized by an organism 

 which does not use the formation of uric acid as an excretory mechanism. 

 The existing evidence thus points to a possible central role of inosinic acid 

 not only in uric acid formation but also in the biosynthesis of polynucleotide 

 purines. 



Studies on the enzjonic formation of adenosine-5-phosphate, which might 

 be connected with the biosynthesis of the purines of nucleic acids, have in- 

 dicated that this compound can be formed from adenosine^^ or adenine.^^ 

 The synthesis from adenine-C^* was examined in pigeon liver homogenates 

 by Goldwasser,^® and the formation of isotopic adenosine diphosphate and 

 triphosphate as well as of adenosine-5-phosphate was demonstrated. The 

 formation of acid-soluble radioactive adenine derivatives from adenine-C^* 

 by rat hver cells in vitro has also been demonstrated by LePage.'^^ 



A central role of adenine in the biosynthesis of nucleic acid purines was 

 originally postulated by Brown. ''^ Brown el alP had found that adenine-N^^ 

 was incorporated into the purines of nucleic acids, while earlier experiments 

 by Plentl and Schoenheimer^ had demonstrated the nonutilization of gua- 

 nine-N^*. This type of experiment, in which labeled purines, nucleosides, 

 or nucleotides were used as precursors, does not, of course, represent a 

 de novo synthesis of the purine ring. Their importance for purine biosynthe- 

 sis lies in the fact that the results may give indications as to which purine 

 compound is synthesized first from small molecules and may establish a con- 

 nection between inosinic acid and nucleic acid purines. Such experiments 

 will, therefore, be briefly discussed here although they are dealt with in 

 greater detail in Chapter 25. 



The concept that adenine is the first nucleic acid purine formed during biosyn- 

 thesis in all cases was disputed by Reichard^^ on the basis of the results obtained 

 with glycine-N'^. When the incorporation of the isotopic nitrogen into nucleic 

 acid adenine and guanine was studied, in man}' organs a larger amount of N'^ was 

 found in the purine ring of guanine than in that of adenine. This was taken as evidence 

 that several biosynthetic pathways leading to polynucleotide purines might exist, 

 one of which did not include the transformation of adenine to guanine. 



" A. Romberg and W. E. Pricer, Jr., J. Biol. Chem. 193, 481 (1951). 

 " E. Goldwasser, Nature 171, 126 (1953). 

 " G. A. LePage, Cancer Research 13, 178 (1953). 



'8 G. B. Brown, Cold Spring Harbor Symposia Qvant. Biol. 13, 43 (1948). 

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

 469 (1948). 



