182 S. S. COHEN 



Tlie synthesis of thymine, or 5-methyl uracil, is of critical interest in DNA 

 metabolism, since this base is fomid uniquely in this nucleic acid. Existing 

 evidence (Friedkin and Kornberg, 1957; Cohen et al., 1957) indicates that in 

 E. coli the methyl group is added to uracil only at the nucleotide level. 



It appears likely that this is true in other organisms as well, although an 

 enzyme is known for the phosphorylation of thymidine; the latter may be 

 thought of as a scavenging system. The utilization of pyrimidine nucleosides 

 via a comparable kinase action is well known, although few organisms are 

 capable of extensive incorporation of free pyrimidmes to nucleic acid. 

 Tumors are an exception to this rule, although it is not entirely clear whether 

 this reflects an augmented complement of pyrimidine phosphorylases or 

 pyrophosphorylases in tumor ceUs or a reduced rate of degradation of free 

 pyrimidines (Canellakis, 1957c). In the mammal, uracil and thymine are rapidly 

 reduced and the pyrimidine ring is then cleaved, as shown in formula (XXX). 



O OH 



CKCH3 

 NH3 + CO2 + 



H2N^ 



Dihydrothymbe y3-amlnoisobutyric 



acid 



.CH2 



(XXX) 



The product of thymine degradation, ^-ammoisobutyric acid, is often 

 excreted and may prove to be a sensitive measure of thymine metabolism 

 and DNA degradation resultmg from radiation therapy and cellular necrosis. 



The enzymatic synthesis of thymidylic acid has been shown to occur as 

 shown in formula (XXXI) (Friedkin and Kornberg, 1957), 



+ HCHO 



+Tetrahydrofolic acid 



Deoxvribose-S'-P Deoxyribose-5 -P 



deoxyuridylic acid thymidylic acid 



(XXXI) 



