BIOSYNTHESIS OF NUCLEIC ACIDS 383 



oxyribosyl derivatives. ^^^ Interchanges are possible between individual 

 deoxyribosyl derivatives^^^ -^^ by transglycosidation mechanisms. 



2. The Alternative Metabolic Fates of Administered 

 Compounds 



The majority of compounds investigated in attempts to elucidate the 

 character of the larger intermediates involved in the assembly of poly- 

 nucleotides have perforce been breakdown products of the polynucleotides, 

 or closely related compounds. In many cases these are not normally present 

 in the animal, or at least are of necessity administered in unphysiological 

 quantities. The extent of anabolism, if any, of a given base or its nucleoside 

 or nucleotide into a derivative which is on a pathway leading to polynu- 

 cleotides will depend upon the balance between its susceptiblity to catabolic 

 enzymes and the rapidity of its anabolism. 



a. Correlations with Known Mammalian Enzymes 



It is probabh^ premature to attempt to relate the existence of metabolic trans- 

 formations in intact organisms to the presence of known enzymes. However, despite 

 duplication of material discussed in greater detail in Chapters 15 and 24, a few cor- 

 relations seem of interest. 



The scarcity of tissue pyrimidine nucleosidases (Chapter 15) correlates with the 

 utilization of pyrimidine ribosyl derivatives.^''^*'®' 



In the rat the deficiency of adenase^'*"'*" and the slow action of xanthine oxidase 

 on adenine^'' permit adenine to survive''^ for anabolic fates, while the abundance of 

 guanase and of xanthine o.xidase correlates with the preferential catabolism to 

 allantoin of guanine,'''''* hypoxanthine, and xanthine. ''^ 2,6-Diaminopurine is also 

 not deaminated by an extract of rat liver acetone powder. i'" The failure to detect the 

 formation of free adenine (by "trapping" it as 2,8-dioxyadenine) after adenosine-8- 

 C* (or inosine) administration^^ is also in harmony with the lack of enzymes which 

 would be expected to yield adenine from adenosine. 



With the purine nucleosides the preferential catabolism of guanosine^' can be 

 attributed to the presence of nucleoside phosphorylase (Chapters 15 and 24), but the 

 survival of some exogenous inosine for anabolic fates might be explained by assuming 

 a balance in favor of anabolism. The partial catabolism of adenosine and of 2,6-di- 

 aminopurine riboside'*' by adenosine deaminase (Chapter 15) might be correlated 

 with the fact that they are less extensively anabolized than the corresponding pu- 



''5 R. Ben-Ishai, E. D. Bergmann, and B. E. Volcani, Nature 168, 1124 (1951). 



'76 M. Friedkin and H. M. Kalckar, /. Biol. Chem. 184, 437 (1950). 



1" W. S. McNutt, Biochem. J. 50, 384 (1952). 



'^8 E. J. Conway and R. Cooke, Biochem J. 33, 457 (1939). 



'^8 D. A. Richert and W. W. Westerfeld, J. Biol. Chem. 184, 203 (1950). 



'8° J. Kream and E. Chargaff, J. Am. Chem. Soc. 74, 4274 (1952). 



•8' H. Klenow, Biochem. J. 50, 404 (1952). 



'82 F. S. Philips, J. B. Thiersch, and A. Bendich, J. Pharmacol. Exptl. Therap. 104, 



20 (1952). 

 183 D. A. Clarke, J. Davoll, F. S. Philips, and G. B. Brown, J. Pharmacol. Exptl. 



Therap. 106, 291 (1952). 



