348 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



was detected. The 4-amino-5-iinidazolecarboxamide is also well utilized for 

 polynucleotide purine synthesis by the rat.*® 



Lowy et al}^ investigated the incorporation of the nucleosides of several 

 of these purines. 2 , 6-Dianiinopurine riboside was incorporated into poly- 

 nucleotide guanine with only a trace conversion to polynucleotide adenine 

 observed. The 2 , 6-diaminopurine riboside was utilized only about one- 

 third as extensively as was the free purine, Crotonoside (isoguanine riboside) 

 was incorporated to the same small extent as was guanosine. Inosine was 

 utilized for both adenine and guanine synthesis but only about one-third as 

 readily as was adenosine. 



d. The Maintenance of the Integrity of the Purine Skeleton 



None of the evidence available has indicated a significant metabolic 

 lability of individual positions of the skeleton of intact purines. 



The conversion in the rat of adenine-l,3-N2'^ into guanine with the isotope in the 

 guanidine portion first suggested^^^'i' that that conversion was accomplished with 

 the retention of the intact purine ring. 2,6-Diaminopurine-2-ammo-l,3-N3>^ showed 

 a similar behavior, and diaminopurine-2-C'' also led" to guanine with the bulk of the 

 C found in the guanidine derived from the 2-position of the guanine. A discussion" 

 of the possible metabolic lability of position 2 of diaminopurine involved the assump- 

 tions that a small discrepancy in the C" values was experimentally significant, and 

 that the over twofold difference in the incorporations of J*J'^ and C" diaminopurine 

 in different groups of rats was also significant. This latter difference between indi- 

 viduals is, however, less than the threefold difference which was observed''* for the 

 incorporation of adenine in different individuals maintained under nominally iden- 

 tical experimental conditions. 



The essential integrity of the purine ring is also demonstrated by the parallel 

 incorporation (with the C'^ always slightly lower) of the isotopes of adenine-1,3- 

 Na'^-S-C'^ into each of the adenylic and guanylic acid isomers in the rat,^* by the 

 identical incorporation and conversion into adenine of guanine-2-C^^ or of guanine- 

 8-C'^ in L. leichmanii ,*^ and by the nonincorporation of N'^Hs of the medium into the 

 ring nitrogens of exogenous purines in Escherichia coli.^" In a variety of experiments 

 in L. casei no metabolic lability of either the 2- or 8-positions of the purines was 

 indicated.^" Specific investigations using formate in the pigeon and the chick*' and 

 in folic acid-deficient rats," and glycine in the mouse,*' did not indicate any unusual 

 lability of individual positions of the purine ring. The precision of most of the ex- 

 perimental evidence leaves something to be desired, but the deviations are not suffi- 

 cient to suggest that there is any appreciable lability of the ring. 



" C. S. Miller, S. Gurin, and D. W. Wilson, Science 112, 654 (1950). 



"M. Gordon, Science 114, 110 (1951). 



« D. H. Marrian, V. L. Spicer, M. E. Balis, and G. B. Brown, /. Biol. Chem. 189, 



533 (1951). 

 ^' F. Weygand, Abstr. 2nd Intern. Congr. Biochem., Paris p. 96 (1952). 

 *» A. L. Koch, F. W. Putnam, and E. A. Evans, Jr., /. Biol. Chem. 197, 105, 113 (1952). 

 " W. H. Marsh, /. Biol. Chem. 190, 633 (1951). 



" G. R. Drysdale, G. W. E. Plant, and H. A. Lardy, J. Biol. Chem. 193, 533 (1951). 

 " C. Heidelberger and G. A. LePage, Proc. Soc. Exptl. Biol. Med. 76, 464 (1951). 



