The formation of cytidine nucleotides and RNA cytosine from orotic acid by the Novikoff tumor in vitro.

The utilization of orotic acid for the formation of RNA ~ uracil has been extensively studied in intact animals, tissue slices, and cell suspensions (reviewed in Refs. 5, 31). The mechanism of the utilization, via the initial conversion of orotic acid to uridine nucleotides and the incorporation of uridine nucleotides into polynucleotides, has been partially described in intact animals (13, 17) and studied in detail in enzyme systems of microbial, avian, and mammalian origin (18, 36) (reviewed in Refs. 33, 38, 39). The concomitant conversion of orotic acid to RNA cytosine has usually been observed in intact cell systems, in vivo and in vitro, but is smaller, more variable, and apparently of secondary nature as compared with the conversion to RNA uracil (1, 7, 13, 14, 16, 18, 33, 34). Lieberman (35) has demonstrated the direct amination of uridine triphosphate to form cytidine triphosphate; the enzyme system, purified from Escherichia coli, required ammonia and ATP. The existence of this reaction suggests strongly that the uridine nucleotides and cytidine nucleotides are involved as intermediates in the conversion of orotic acid to RNA cytosine. Evidence has more recently been offered that