BIOSYNTHESIS OF PURINES AND PYRIMIDINES 



305 



TABLE XII 

 Biosynthesis of Orotic Acid in Liver Slices" • '"^ 



" Experimental conditions as in Table XI. 



'' 32 atom % excess N". 



'^ Isolated after addition of 100 mg. DL-ureidosuccinic acid as carrier. 



was labeled with N^^ This substance, therefore, seems to be a direct pre- 

 cursor of orotic acid in the liver slice system. This was confirmed by the 

 incorporation of labeled L-ureidosuccinic acid into orotic acid. 



Bicarbonate-C^^ was preferentially incorporated into position 2, as might 

 be expected from the results of Heinrich and Wilson,*^ who showed the cor- 

 responding incorporation into uracil. 



L-aspartate-l,4-C'^ donated its isotope almost exclusively to the carbons 

 of positions 6 plus 7, while the label of L-aspartate-2,3-C''* showed up mainly 

 in positions 4 plus 5. The relatively low incorporation of the isotopic aspar- 

 tic acids, compared with ammonia-N^^ or N^^-labeled ureidosuccinic acid, 

 is explained on the basis of permeability barriers for aspartic acid in the 

 liver. In the case of bicarbonate the low incorporation is explained by the 

 continuous exogenous administration of unlabeled CO2 . 



A likely reaction sequence for the synthesis of orotic acid is represented 

 by Fig. 12. Nothing is known about the source of the nitrogen for position 1 

 (c/. addendum). 



Few data exist on the connection between orotic acid and polynucleotide 

 pyrimidines. Of interest in relation to this is the demonstration by Hurl- 

 bert and Potter '^^ and by Hurlbert'^^'^^^ of the existence of acid-soluble, 

 radioactive pyrimidine derivatives in rat liver after the administration of 



1" R. B. Hurlbert and V. R. Potter, /. Biol. Chem. 195, 257 (1952). 

 "2 R. B. Hurlbert, Federation Proc. 11, 234 (1952). 

 133 R. B. Hurlbert, Federation Proc. 12, 222 (1953). 



