390 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



soluble fraction. However, in view of the uncertainty as to the character of 

 the "active adenine," and of the complexity of the acid-soluble nucleo- 

 tides,"^ '^'''•^^' including those of muscle,^' '^^^'^-^ decision must be reserved as 

 to the relationship of the currently recognized metabolites in the acid- 

 soluble fractions to the actual "active" polynucleotide precursors. 



h. The Possible Positions of Mono- or Oligonucleotides as Polynucleotide 

 Precursors 



In the intact animal, purine and pyrimidine nucleotides have, in every 

 case except that of the adenylic acids, been found to be utilized as readily 

 as, or more extensively than, any of the simpler derivatives. Guanylic acid 

 commands particular attention, for in the rat its purine moiety can be uti- 

 lized far more readily than can any of the simpler derivatives. 



The recent observation that the P^^ of either guanosine-2'- or -3 '-phos- 

 phate-?^' administered to the rat was greatly diluted and was almost uni- 

 formly distributed between the individual nucleotides of the PNA^"" sug- 

 gests that, despite the virtue of the phosphorylated derivative as a 

 precursor, it may not be incorporated in toto. It does seem that the 2'- or 

 3 '-nucleotide is simply a susceptible substrate and that it is further anab- 

 olized into the "active" precursor with the eventual loss of the original 

 phosphorus. 



It is possible that an individual phosphate introduced into a polynucleotide as 

 part of one nucleotide might, upon alkaline hydrolysis, be removed as part of the 

 nucleotide derived from the adjacent base. However, the present concepts of a 

 grouping of the purines and of the pyrimidines in the polynucleotide structure 

 (Chapter 12) would not suggest that complete randomization of the phosphate could 

 be expected in the course of alkaline hydrolysis. Future experiments involving enzy- 

 mic degradation of the nucleic acids can possibly avoid that ambiguity. 



The ability of the rat to incorporate free adenine more extensively than 

 the 2'-, 3'-, or 5'-nucleotides is also suggestive that none of those nucleotides 

 represent the "active" derivative which arises from the free adenine. From 

 the results in the rat, no particular importance can be attached to any one 

 of the isomeric nucleotides. However, the specific growth responses of sev- 

 eral microorganisms to the 3'-isomers, their preferential utilization by L. 

 casei under conditions where they are not required for growth (Fig. 6), and 

 particularly the utilization of 3'-adenylic acid by the L. casei mutant which 

 utilizes adenine very poorly ,^^ suggest that the 3'-phosphates may have some 

 special significance. Such a notion is in harmony with the importance of 

 the 3'-linkage in polynucleotides (Chapter 12). The information from 



"1 J. Sacks and L. Lutwak, Federation Proc. 12, 468 (1953). 



"2 O. Snellman and B. Gelotte, Nature 168, 461 (1951). 



2" P. A. Khairallah and W. F. H. M. Mommaerts, Circulation Research 1, 8, 12 (1953). 



