BIOSYNTHESIS OF PURINES AND PYRIMIDINES 295 



This has been demonstrated for PNA by many investigators"*^'^*''* and for DNA by 

 Bendich et a/.'' It is quite possible that this heterogeneity might influence the biosyn- 

 thesis of purines. The results of Abrams'* with a purine-requiring yeast mutant might 

 be explained on this basis. He showed that this mutant was still capable of a de novo 

 synthesis of PNA purines from glycine-1-C'^ even though it required preformed 

 purines in the medium for growth. 



Furthermore, Brown et al.^^ have shown that the incorporation of adenine into 

 DNA is only a verj'^ small fraction of that into PNA in the rat (ratios for DNA- 

 adenine/PNA adenine from 1 : 29 to 1 : 73 have been reported), while results by Reich- 

 ard'*'"" with glycine-Ni* gave much higher corresponding ratios (1 : 2 to 1 : 4). Similarly 

 high ratios with labeled small molecules as precursors have been demonstrated with 

 formate-C'^''* serine-3-C'^,^* and gh-cine-2-C'*.^* In order to rule out the factor of 

 differences in e.xperimental conditions, Furst and Browni"" administered adenine-C^^ 

 and glycine-N'* simultaneously. The same discrepancy in incorporation ratios was 

 found. Two synthetic pathwaj's for polynucleotide purines seem to exist, one repre- 

 sented by the incorporation of adenine and the other b\' the de novo sj'nthesis of 

 purines from small molecules. This problem is discussed more fully in Chapter 25. 



II. Biosynthesis of Pyrimidines 



The wealth of data which has accumulated on the biosynthesis of purines 

 greatly exceeds that available for the biosynthesis of pyrimidines. One rea- 

 son for this is undoubtedly the fact that in pyrimidine biogenesis there is 

 no known substance which can play a role equivalent to that of uric acid 

 and hypoxanthine in the elucidation of purine synthesis. At an early date 

 Cerecedo^"^ demonstrated that pyrimidines are cataboUzed to urea by the 

 dog. These results have been confirmed by Plentl and Schoenheimer,^ who 

 found that thymine-N^^ and uracil-X^° give rise to urea-N^^ in the rat. Re- 

 cently another possible catabolic mechanism in the rat has been found by 

 Fink e^ aZ./°^ who demonstrated the excretion of jS-aminoisobutyric acid 

 in the rat after the feeding of thymine or DNA. These mechanisms are 

 hardly suited for precursor studies. 



On the other hand, the formation of orotic acid in rat liver slices, as dem- 

 onstrated by Reichard,^''^ has proved valuable as a model system for pyrimi- 

 dine synthesis. '°^ The results obtained with this system will be discussed 

 in the section on orotic acid. 



" R. Jeener, Nature 163, 837 (1949). 



8« C. P. Barnum and R. A. Huseby, Arch. Biochem. 29, 7 (1950). 



" A. Bendich, P. J. Russell, Jr., and G. B. Brown, /. Biol. Chetn. 203, 305 (1953). 



'8R. Abrams, J. Am. Chem. Soc. 73, 1888 (1951). 



'" G. B. Brown, M. L. Petermann, and S. S. Furst, /. Biol. Chem. 174, 1043 (1948). 

 '0° S. S. Furst and G. B. Brown, /. Biol. Chem. 191, 239 (1951). 

 '«' L. R. Cerecedo, J. Biol. Chem. 88, 695 (1930). 



'"2 K. Fink, R. B. Henderson, and R. M. Fink, J. Biol. Chem. 197, 441 (1952). 

 i«3 P. Reichard, J. Biol. Chem. 197, 391 (1952). 

 '»^ P. Reichard and U. Lagerkvist, Acta Chem. Scand. 7, 1207 (1953). 



