284 



PETER REICHARD 



TABLE V 

 Synthesis of Hypoxanthine in Pigeon Liver Extracts from Different N'^ 



Precursors^* 



N'* precursor 



NH4CI 



Aspartic acid 



Glutamic acid 



Glutamine (amide N^*) 

 Glycine 



Moles N'* utilized for 



hypoxanthine synthesis 



per mole of C'*-labeled 



glycine 



0.27 

 1.20 

 1.20 

 1.90 

 1.00 



N'* concentration (atom per 



cent excess) in hypoxanthine 



nitrogen no. 



1+3 7 + 9 



0.091 

 0.185 

 0.186 

 0.058 



0.009 

 0.025 

 0.176 

 0.378 



0.018 

 0.750 



9 



0.334 

 0.058 



of the earlier finding of Schulman et al.^^ that in these extracts CO2 , gly- 

 cine, and formate react in the molecular proportions of 1:1:2 to give one 

 molecule of hypoxanthine. The N^ ^-labeled precursors tested were incu- 

 bated together with glycine- l-C^^ in the pigeon liver extracts and the 

 hypoxanthine formed was analyzed for C^* and N'^ The C" content of 

 hypoxanthine measured the de novo synthesis of this purine, and from the 

 ratio of C^'* to W^ in the hypoxanthine the number of N^^ atoms contrib- 

 uted from each nitrogenous compound to one molecule of hypoxanthine 

 could be calculated. It was found that one atom of N^^ was contributed 

 from glycine, glutamic acid, or aspartic acid, and two atoms of W^ from 

 the amide group of glutamine. By degradation it was shown that the N^^ 

 from glycine was located in position 7, that from glutamic or aspartic acids 

 in the sum of positions 1 and 3, and those from glutamine in position 9 

 as well as in the sum of positions 1 and 3 (Table V). 



When these results are compared with those obtained by Lagerkvist 

 with ammonia-N^^ in pigeons it seems probable that the amide group of 

 glutamine is the nitrogenous precursor of positions 3 and 9. Thus aspartic 

 or glutamic acid must donate the nitrogen of position 1. Lagerkvist's re- 

 sults with Ni5-labeled aspartic acid in vivo are probably explained by the 

 many side reactions taking place in such a complex system and by the 

 relative impermeability of the liver to aspartic acid. 



Fig. 3 gives a summary of the different carbon and nitrogen precursors 

 for uric acid as far as they are known at the present time. 



h. Polynucleotide purines 



A paper by Barnes and Schoenheimer^ contains the first definite indica- 

 tion that the heterocyclic purine molecule can be synthesized from simple 

 molecules. These authors showed that after the administration of W^- 



