BIOSYNTHESIS OF NUCLEIC ACIDS 363 



PNA's, although in some instances the nuclear PNA has been studied sepa- 

 rately. 



With formate the appreciable renewal of the PNA of brain indicates that the lack 

 of incorporation into brain DNA in the same experiment (Table II, columns 9 and 10) 

 does not need to be attributed to an impermeable barrier. The large renewal of the 

 kidney PNA, coupled with the low renewal of its DNA, gives it the highest ratio 

 between the renewals of PNA and DNA of any of these organs except brain. Small 

 variations between the renewals observed in liver, pancreas, and testis, and the 

 reversal of the ratio of incorporation into adenine and guanine in spleen in the two 

 experiments remain unexplained. 



For liver and intestinal PNA's the relative incorporations of several pre- 

 cursors are available (Table IV). There is a considerably greater incorpora- 

 tion of those precursors which are involved in the synthesis de novo of the 

 carbon-nitrogen skeleton of the purines into the intestinal PXA than into 

 the hver PNA, and this is in striking contrast to the approximately equal 

 or greater incorporation of administered adenine into the PMA of the hver 

 as compared to intestine. Thus with formate, ammonia, or glycine the 

 ratios for the incorporation into the PNA of hver and of the intestine, either 

 into the adenines or the guanines, range from 0.38 to 0.11. On the other 

 hand, the corresponding liver-to-intestine ratios for the incorporation of 

 adenine are 1.65 to 0.75. Two double-labeling experiments, one involving 

 simultaneous administration of formate-C^^ and adenine-1 ,3-N2^* (hne 8),^^ 

 and the other glycine-l-C^^ and adenine-2-C'^ (hne 7)^^ have been performed 

 and each unequivocally confirms the differences in the behaviors of the 

 respective purine precursors relative to that of the preformed purine. The 

 absolute incorporation of adenine was slightly greater in the intestinal PNA 

 in one investigation (line 7), but the fact that the quantity of adenine used 

 there was 9.5 times that used in the other (hne 8) may have been a factor. 

 Verification of the facile incorporation of adenine into hver PNA also comes 

 from comparison of lines 6 and 7, where the large dose of adenine adminis- 

 tered brought about in the liver a far more pronounced sparing, or inhibi- 

 tion, of glycine utihzation that it did in the intestine. With orotic acid, 16 % 

 of the dose was found in rat liver PNA and but 1.5 % in the remaining vis- 

 cera at 20 hours, ^" and it appears that this pyrimidine precursor is also 

 readily incorporated into liver PNA. The behavior of phosphate (hne 10) 

 is, curiously enough, more analogous to that of adenine than to that of the 

 smaller precursors. 



The marked contrasts between the incorporations of preformed adenine 

 and those of glycine and formate into hver and intestinal PNA's forcibly 

 emphasize the fact that experiments with a single "tracer" cannot be relied 

 upon to measure the intrinsic metabolic activity of even the purine moieties, 

 much less of the whole nucleic acid molecule. 



