NUCLEOTIDES I37 



Synthesis of purines 



Though the synthesis of the nitrogenous bases and the 

 pentose sugars is here, for convenience, considered separ- 

 ately, such a division does not imply that the synthesis of 

 nucleotides necessarily proceeds by the phosphorylation of 

 a nucleoside formed by the joining together of the pre- 

 formed base and the pentose sugar. There is some experi- 

 mental evidence that glycosidation of a precursor precedes 

 completion of the heterocyclic ring systems found in purines 

 and pyrimidines. Moreover, the possibility must always be 

 borne in mind that the routes of synthesis are not the same 

 in diiferent species. Experiments with substances labelled 

 with isotopes have revealed that Esch. coli and yeast resemble 

 mammals in that they synthesize purines and pyrimidines 

 from relatively simple precursors, namely CO 2, NH3, for- 

 mate and glycine. In the synthesis of guanine by yeast, C-4 

 is derived from CO 2, C-2 and C-8 from formate or sub- 

 stances which give rise to formate (e.g. serine, the methyl 

 group of methionine), C-6, C-5 and N-7 from the carboxyl, 

 methene and amino-N of glycine respectively, and the re- 

 maining nitrogen atoms from NH3 [20]. The utilization of 

 other compounds for purine synthesis is indirect and in- 

 volves their prior conversion to CO 2, NH3, glycine or for- 

 mate. Only one of the intermediates between these simple 

 precursors and the completed purine is known. When Esch. 

 coli is grown in the presence of sub-bacteriostatic concentra- 

 tions of sulphanilamide or the folic acid analogue N-10- 

 methylpteroylglutamic acid, an amine identified as 4- 

 amino-imidazole-5-carboxamide (AIC) accumulates in the 

 medium [49]. This substance only requires the addition of 

 one carbon atom (corresponding to position 2) to complete 

 the purine ring, and since it can be utilized by yeast, 

 Lh. arahinosus and purine auxotrophs of Esch. coli and 

 Ophiostoma, it is reasonable to suggest that it is a natural 

 intermediate in purine synthesis. If glycine, a known pre- 

 cursor in purine synthesis, is added to the medium, produc- 

 tion of the amine is increased [45], whereas it is reduced by 

 methionine, especially if trace amounts of PAB are present, 

 and also by vitamin B;^,- Moreover, in the absence of purines, 



