Regulation in mammals is not well understood. A single protein that consists of three identical subunits catalyzes the first three steps of the synthesis. The last two steps are catalyzed by another multifunctional enzyme. Pyrimidine nucleotides decrease the aspartate transcarbamoylase and dihydroorotase activities of the multifunctional enzyme, but the molecular basis for the decrease in activity is unknown. A genetic disorder of pyrimidine biosynthesis.
Orotic acid accumulates in the blood and is excreted in the urine.
Orotic aciduria is alleviated by feeding of uridine or cytidine. Salvage pathways for pyrimidine nucleotides. The free pyrimidine bases that result from nucleotide degradation are uracil and thymine. Uracil can be converted to UMP by two sequential reactions. The first reaction is the reverse of a reaction that occurs in degradation of nucleotides.