Considering the patient in question 3, orotic acid levels
are high in this patient due to which of the following?
ExplanationThe rate-limiting step for de novo pyrimidine synthesis is carbamoyl phosphate synthetase II (CPS-II), which produces carbamoyl phosphate in the cytoplasm. In an OTC deficiency, the carbamoyl phosphate produced in the mitochondria leaks into the cytoplasm, leading to orotic acid synthesis as the regulated step of the pathway is being bypassed. The elevated ammonia is not a substrate of CPS-II, and while glutamine is also elevated, and is a substrate of CPS-II, higher glutamine concentrations will not overcome enzyme inhibition by its allosteric inhibitor, UTP. Aspartate transcarbamoylase is the regulated step of pyrimidine biosynthesis in many prokaryotic cells, but not in humans. This step is necessary for pyrimidines to be synthesized starting with carbamoyl phosphate.
