36. BIOSYNTHESIS OF PYRIMIDINE NUCLEOTIDES 329 



Jobling carcinoma is consistent with a prior dephosphorylation and equili- 

 bration with inorganic phosphate. Roll et a/. 46 have confirmed this result 

 for a number of rat tissues using pyrimidine-3' (2'-) -ribonucleotides uni- 

 formly labeled with C 14 and with P 32 . The nucleoside units of the nucleotides 

 were, however, incorporated extensively into tissue ribonucleic acid (RNA) 

 without rupture of the glycoside linkage. Extracellular nucleotides are 

 utilized for E. coli nucleic acids only after dephosphorylation, the nucleo- 

 tide-P being equilibrated with the inorganic phosphate of the medium. 46 



In contrast to the negligible utilization of free pyrimidines for rat liver 

 polynucleotide formation, Rutman et al. 40 have shown that uracil-2-C 14 is 

 incorporated into the RNA of hepatomas induced by 2-acetylaminoflu- 

 orene. Heidelberger et al. 47 have demonstrated a similar precursor role of 

 uracil-2-C 14 in rat intestinal mucosa and in the Flexner-Jobling carcinoma. 



Canellakis 48 has recently reinvestigated the incorporation of uracil by 

 rat tissues. At low extracellular concentrations, uracil, uridine, and uridine- 

 5'-phosphate are extensively degraded to CO 2 by rat liver slices. In contrast 

 to this and to previous results uracil at high extracellular concentration is 

 utilized as effectively as uridine or uridine-o'-phosphate for polynucleotide 

 synthesis. In agreement with these observations Canellakis 49 has demon- 

 strated the occurrence in a high-speed supernatant fraction of rat liver of 

 a uridine phosphorylase (cf. Cardini et al., b0 Paege and Schlenk 51 ) and a 

 uridine kinase which together define a pathway for uracil utilization (Fig. 

 2). Cytosine is not a substrate of the phosphorylase. The same supernatant 

 fraction also contains the catabolic enzymes degrading uracil to CO2 via 

 4,5-dihydrouracil, 0-ureidopropionic acid, and ^-alanine 52 (cf. Grisolia and 

 Wallach, 53 Fink et a/., 54 Fritzson, 55 and Fritzson and Pihl 56 ). It would ap- 

 pear that there is an inverse relationship between the RNA turnover of a 

 tissue and its content of the uracil catabolic enzymes. It is suggested that 

 the balance between the anabolic and catabolic pathways may constitute 

 part of a homeostatic mechanism governing the rate of RNA synthesis. 



46 P. M. Roll, H. Weinfeld, and E. Carroll, J. Biol. Chem. 220, 455 (1956). 



47 C. Heidelberger, K. C. Liebman, E. Harbers, and P. M. Bhargava, Cancer Re- 

 search 17, 399 (1957). 



48 E. S. Canellakis, J. Biol. Chem. 227, 701 (1957). 



49 E. S. Canellakis, J. Biol. Chem. 227, 329 (1957). 



so C. E. Cardini, A. C. Paladini, R. Caputo, and L. F. Leloir, Acta Physiol. Latino- 



amer. 1, 57 (1950). 

 31 L. M. Paege and F. Schlenk, Arch. Biochem. Biophys. 52, 488 (1954). 



52 E. S. Canellakis, J. Biol. Chem. 221, 315 (1956). 



53 S. Grisolia and D. P. Wallach, Biochim. et Biophys. Acta 18, 449 (1955). 



54 R. M. Fink, C. McGaughey , R. E. Cline, and K. F. Fink, J. Biol. Chem. 218, 1 (1956) . 

 65 P. Fritzson, J. Biol. Chem. 226, 223 (1957). 



56 P. Fritzson and A. Pihl, J. Biol. Chem. 226, 229 (1957). 



