CHAPTER 23 



Biosynthesis of Purines and Pyrimidines 

 PETER REICHARD 



Page 



I. Biosynthesis of Purines 277 



1. Synthesis from Small Molecules 277 



a. Biosynthesis of Uric Acid and Hypoxanthine 277 



(1) Carbon Precursors 278 



(2) Nitrogen Precursors 281 



b. Polj'nucleotide Purines 284 



2. TheRoleof the Carboxamide and the Enzymic Synthesis of Inosinic Acid 287 



3. Interconversion of Purines 292 



II. Biosynthesis of Pyrimidines 295 



1. Small Molecules as Precursors 296 



2. The Function and Biosynthesis of Orotic Acid 299 



III. Addendum 306 



I. Biosynthesis of Purines 



1. Synthesis from Small Molecules 



Early concepts of the biosynthesis of purines are mainly of historical 

 interest. It has been clear for a long time that higher organisms can syn- 

 thesize purines de novo from other molecules. In Miescher's classical ex- 

 periments large amounts of nucleic acid in the sperm were synthesized by 

 the male salmon while muscle protein was disappearing. During growth 

 young animals synthesize nucleic acids and nucleotides while exclusively 

 on a milk diet containing only traces of purines. Many similar examples 

 can be found. 



a. Biosynthesis of uric acid and hypoxanthine 



Uric acid is the chief end-product of all nitrogen catabolism in birds and 

 reptiles. In man and the higher apes relatively small amounts of uric acid 

 are found in the urine, and it has been assumed that in these cases uric 

 acid is more specifically the end-product of purine catabolism (see Chapter 

 26). 



Early studies on the biosynthesis of purines usually involved the clas- 

 sical feeding technique, in which different substances were fed to the fast- 

 ing animal and the quantitative excretion of uric acid studied. Alanine,' 



1 H. B. Lewis, M. S. Dunn, and E. A. Doisy, J. Biol. Chem. 36, 9 (1918). 



277 



