BIOSYNTHESIS OF NUCLEOSIDES AND NUCLEOTIDES 325 



the assembling of nucleotides may begin with the production of pentose- 

 phosphate and its combination with simple nitrogenous compounds, leading 

 to ahphatic ribotides.^^'^'^'^°'* The nitrogenous system is finished afterwards 

 by addition of the necessary structure, followed by ring closure (see Chap- 

 ter 23). According to this concept, nucleosides and free bases play no part 

 in anaboUsm ; they are products of catabolism only as indicated in the fol- 

 low ing scheme: 



Purine precursors —* Precursor riboside -^ Precursor ribotide 



U . (19) 



(Uric acid, etc.) <— Purine ^ Purine riboside :;=^ Purine ribotide 



Inosinic acid appears to be the key intermediate; adenylic acid and guanylic 

 acid may be formed from it by the reactions discussed in Section II. 8. 

 Opponents of this concept emphasize that nucleoside phosphorylase and 

 adenosine phosphokinase action provide a plausible route of nucleotide 

 synthesis with adenylic acid as a primary product. In both instances, ex- 

 periments have been restricted so far to the purine ribose compounds. A 

 decision in favor of one of these alternatives or the assumption of multiple 

 pathways would be premature at this time in view of the limited experi- 

 mental data which are available. 



1. Experiments with Labeled Nucleosides and Nucleotides 



In the formulation of an acceptable metabolic scheme, one may look for 

 guidance from the results of tracer experiments. Most of this work has been 

 done with labeled bases, and, among other results, it has brought to Hght 

 the strict separation of purine and pyrimidine metabolism. 



Experiments with labeled nucleosides are not so numerous, because these 

 compoiinds are more difficult to prepare; biosynthesis of them is usually 

 employed. ^^'" Parenteral administration to animals and incorporation into 

 microbiological growth media have shown that they are incorporated into 

 nucleic acids. In rats the purine nucleosides were less effectively incor- 

 porated than adenine,^* but the reverse is true for pyrimidine nucleosides 

 compared with free pyrimidines. Table I shows some data of Lowy et al.,''^ 

 which indicate that the label of adenosine is found in both constituent 



" J. M. Buchanan and M. P. Schulman, J. Biol. Chem. 202, 241 (1953). 



70 G. R. Greenberg, Federation Proc. 12, 651 (1953). 



'«* D. A. Goldthwait and R. A. Peabody, Federation Proc. 13, 218 (1954). 



'1 F. J. DiCarlo, A. S. Schultz, P. M. Roll, and G. B. Brown, J. Biol. Chem. 180, 329 



(1949). 

 " E. Hammarsten, P. Reichard, and E. Saluste, /. Biol. Chem. 183, 105 (1950). 

 " I. A. Rose and B. S. Schweigert, /. Biol. Chem. 202, 635, (1953). 

 ^' P. M. Roll, B. G. Brown, F. J. DiCarlo, and A. S. Schultz, J. Biol. Chem. 180, 333 



(1949). 

 75 B. A. Lowy, J. Davoll, and G. B. Brown, J. Biol. Chem. 197, 591 (1952). 



