Figure 7.

Schematic Overview of Pyrimidine de Novo Synthesis, Salvage, and Degradation.

Nucleotides synthesized de novo enter the nucleotide pool and become further converted to nucleic acids and other metabolic intermediates. Breakdown of nucleotides to uridine and uracil may lead to complete degradation or the resynthesis of UMP in the salvage pathway. Increasing the activity of URH in overexpressor mutants leads to marked stimulation of pyrimidine degradation but not of salvage pathway activity or de novo synthesis. This is illustrated by the insensitivity of mutants with enhanced URH activity toward 5-FO, 5-FD, and 5-FU. 1, Carbamoyl phosphate synthase (CPSase); 2, Asp transcarbamoylase (ATCase); 3, dihydroorotase (DHOase); 4, dihydroorotate dehydrogenase (DHODH); 5, UMP-synthase (UMPSase); CP, carbamoyl phosphate; CA, carbamoyl aspartate; DHO, dihydro-orotate; OA, orotic acid.