BIOSYNTHESIS OF PURINES AND PYRIMIDINES 



299 



Methylamine 

 Fig. 9. Degradation of uracil according to Lagerkvist.^"^ 



was then degraded stepwise according to Phares."* In a separate reaction 

 carbon 2 was obtained as urea by degradation of uracil with permanganate. 

 This method was tested by the degradation of uracil-6-C"-5-C^^ which 

 gave excellent results. 



2. The Function and Biosynthesis of Orotic Acid 



Orotic acid (uracil-4-carboxylic acid, Fig. 10) was discovered in milk by 

 Biscaro and Belloni."^ The simultaneous finding by Loring and Pierce"" 

 and by Rogers'-" that orotic acid can replace pyrimidines as a growth factor 

 for a mutant of Neurospora and for certain streptococci was the first definite 

 indication that this substance might be connected in some way with pyrimi- 

 dine biosynthesis. Investigations with Neurospora mutants were carried on 

 by Mitchell and collaborators.'"' ■'-' From genetic evidence they arrived 

 at the conclusion that orotic acid was not a normal intermediate, but arose 

 in a side reaction during pyrimidine biosynthesis.'^' 



An investigation of the possible significance of orotic acid as a pyrimidine 

 intermediate in the rat was carried out by Arvidson et al}"^"^ and by Reich- 



"8 E. F. Phares, Arch. Biochem. and Biophys. 33, 173 (1951). 



"^ G. Biscaro and E. Belloni, Ann. soc. chim. Milano 11, Nos. 1 and 2 (1905); Chem. 



Zentr. 2, 64 (1905). 

 '20 H. J. Rogers, Nature 153, 251 (1944). 



'2' H. K. Mitchell, M. B. Houlahan, and J. F. Nye, J. Biol. Chem. 172, 525 (1948). 

 '-2 H. Arvidson, N. A. Eliasson, E. Hammarsten, P. Reichard, H. von Ubisch, and 



S. Bergstrom, J. Biol. Chem. 179, 169 (1949). 



