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Orotate phosphoribosyltransferase is an enzyme in the pyrimidine biosynthesis pathway that catalyzes the conversion of orotic acid (orotate) and phosphoribosyl pyrophosphate (PRPP) to orotidine-5'-monophosphate (OMP). In humans, this function is carried out by a domain of the bifunctional enzyme uridine monophosphate synthase (UMPS). Mutations or deficiencies in this enzyme result in the accumulation of orotic acid and can cause orotic aciduria, characterized by megaloblastic anemia and developmental anomalies. OPRTase is also a target of chemotherapeutic agents like 5-fluorouracil, which inhibit pyrimidine nucleotide synthesis essential for DNA and RNA replication in rapidly dividing cells.
Competitive inhibition (5-FU competes at OPRTase active site), inhibition of pyrimidine synthesis
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