BIOSYNTHESIS OF PURINES AND PYRIMIDINES 



297 



COOH 



I 



c=o 



I 



I 

 COOH 



Oxalacetic 

 acid 



H.N' 



"CH 



HN' 



"CH 



^C-COOH 



HN-ribose 



= C ^CH 

 jjq'^ HN-ribose 



HN XH 



I II 



o=a ^CH 



N-ribose 



Uridine 



HN' 



I 



o=a 



"CH 



II 



,C-C00H 



HN' 



I 



o=a 



Orotic acid 



~-N' 

 H 



Uracil 



^:h 



II 



CH 



Fig. 8. Biosynthesis of uridine in Neurospora according to Mitchell and Houlahan."" 



shown not to give reliable results for position 4 of uracil. ^°^ Formate-C^* 

 was not found to be a precursor of uracil.^^ 



Evidence has been obtained that the 5-methyl group of thymine is de- 

 rived from a "1-C" derivative. Totter et al.'^^ found activity in this group 

 using formate-C'^ as precursor, and Elwyn and Sprinson^^ showed that 

 serine-3-C^^ and glycine-2-C^^ also donated their isotope to this methyl 

 group. In contrast to this, LePage and Heidelberger^^ could not find that the 

 isotope was transferred to this group from a-labeled glycine. Elwyn et al.^^^ 

 suggested that the incorporation of the /3-group of serine might not proceed 

 via formate. This suggestion was based on experiments with the /S-group 

 labeled with C^^ and deuterium, in, which the results indicated that both 

 atoms were incorporated as a unit. Oxidation of the group to formate 

 would have diluted the deuterium relative to the C* content. 



From experiments with mutant strains of Neurospora, Mitchell and 

 Houlahan^"^ suggested that the carbon chain of the pyrimidine ring could 

 originate from oxalacetic acid. Because of the better utilization of the 

 nucleosides, as compared with the free pyrimidine bases, as growth factors 

 (Loring and Pierce""), it was proposed that ribosidation ocurred before 

 ring-closure. This theory was very attractive because of the demonstration of 

 a similar situation in the biosynthesis of the purines. However, the experi- 

 mental evidence in the case of the pyrimidines can be equally well ex- 

 plained on another basis, as discussed below. The reaction sequence pro- 

 posed by Mitchell and Houlahan^"^ is demonstrated by Fig. 8. 



107 U. Lagerkvist, Ada Chem. Scand. 7, 114 (1953). 



los D. Elwyn, A. Weissbach, and D. B. Sprinson, /. Am. Chem. Soc. 73, 5509 (1951). 



•<>« H. K. Mitchell and M. B. Houlahan, Federation Proc. 6, 506 (1947). 



'•0 H. S. Loring and J. G. Pierce, /. Biol. Chem. 153, 61 (1944). 



