Orotic Aciduria

 

What happens if there is a defect in the protein chain containing the enzyme activities of the last two steps of the pyrimidine nucleotide synthesis pathway? One would expect a buildup of orotic acid, and this is what happens. The increased excretion of orotic acid in the urine leads to the name of this condition, "orotic aciduria", and this condition is also associated with growth retadration and anemia. It is the only known inherited defect in this pathway, as any other defect would be lethal to the developing fetus. The treatment involves giving uridine and/or cytidine, and the UMP and CMP that result from their phosphorylation inhibit carbamoyl phosphate synthetase II, which  decreases the production of orotic acid.