You are attending to a patient who manifests with orotic aciduria. You suspect a defect in pyrimidine nucleotide biosynthesis, but aside from the orotic aciduria there are no other classical symptoms apparent in this patient, such as megaloblastic anemia, and the activity of UMP synthetase is normal. Which of the following enzymes is most likely deficient in this patient leading to the orotic aciduria?

Question

Quizplus · Accepted Answer

Orotic aciduria can be the result of a deficiency in the urea cycle enzyme ornithine transcarbamoylase (OTC). A deficiency in OTC results in the urea cycle carbamoyl phosphate being transported from the mitochondria to the cytosol. Within the cytosol, the carbamoyl phosphate can serve as an intermediate in pyrimidine nucleotide synthesis, bypassing the regulated rate-limiting step catalyzed by ATCase. This will lead to synthesis in excess of the demands of the cells, resulting in increased orotic acid production.

You Are Attending to a Patient Who Manifests with Orotic