BIOSYNTHESIS OF NUCLEOSIDES AND NUCLEOTIDES 327 



tion of the pyrimidine leading to thymine or one of its homologues is ir- 

 reversible. Rose and Schweigert^^ studied the utihzation of totally labeled 

 cytidine-C" by the rat. It recurs in both the ribo- and deoxyribonucleic 

 acid, and the incorporation does not involve prior cleavage of the glyco- 

 sidic linkage; this favors the concept that a mechanism exists for the con- 

 version of ribose into deoxyribose at the nucleoside or nucleotide level. 



Similar studies have been carried out with a variety of microorganisms 

 such as yeast and bacterial species.''^ ■" '^^ L. casei utihzed purine ribo- 

 sides, but not as effectively as free purines or purine nucleotides." The 

 fragments of uniformly labeled ribonucleic acid, prepared by biosynthesis 

 using the phytoflagellate Euglena gracilis, were tested with E. coli and L. 

 leichmannii?^ Cytosine and cytidine were essentially equivalent as sources 

 of ribonucleic acid pyrimidines, but the ribose of totally labeled cytidine 

 was incorporated less effectively than the base. 



The inferiority of purine ribosides," compared with the nucleotides^^ and 

 the free purine bases, to serve as nucleic acid precursors has been interpreted 

 to indicate that they cannot be intermediates in the conversion of free 

 purines into nucleic acid purines. On the other hand, the possibihty of a 

 primary conversion of nucleosides into the free bases has been excluded.''^'" 

 One may assume that the purines react with ribose- 1,5-diphosphate and 

 that this reaction is faster than the addition of phosphate to preformed 

 nucleosides. A different picture obtains with pyrimidines. The failure of the 

 bases other than orotic acid^^ to be incorporated, and the precursor activity 

 of the nucleosides, suggest a role of the latter as intermediates of nucleic 

 acid formation. 



Observation of overall reactions in cells and tissues by means of tracer 

 techniques fails to reveal detail. On the other hand, in vitro studies have 

 yielded only fragmentary information which is not yet sufficient to map a 

 metabolic scheme. Reactions which may figure prominently in nucleotide 

 synthesis will be discussed below. 



2. Enzymic Reactions of Nucleotide Metabolism 



o. 5 -Nucleotidase and 3 -Nucleotidase 



Phosphatases usually have a wide range of specificity, but the nucleo- 

 tidases are an exception. Evidence of the existence of a specific 5-nucleo- 



" M. E. Balis, D. H. Levin, G. B. Brown, G. B. Elion, H. Vander-Werflf, and G. H. 



Hitchings, /. Biol. Chem. 199, 227 (1952). 

 '8 M. E. Balis, D. H. Levin, G. B. Brown, G. B. Elion, H. Vander-Werff, and G. H. 



Hitchings, J. Biol. Chem. 200, 1 (1953). 

 '8 H. Arvidson, N. A. Eliasson, E. Hammarsten, P. Reichard, H. V. Ubisch, and 



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



