OPRT

OPRT stands for orotate phosphoribosyltransferase, an enzyme that catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribosyl-1-pyrophosphate (PRPP) to orotate, producing orotidine-5'-phosphate (OMP) and pyrophosphate. This reaction is the first committed step in the de novo biosynthesis of pyrimidine nucleotides, providing the substrate that is later converted to UMP and then to other pyrimidines.

In bacteria and many lower organisms, OPRT is a monofunctional enzyme encoded by the pyrE gene. In higher eukaryotes, OPRT activity is typically part of a bifunctional enzyme, orotate phosphoribosyltransferase/ orotidine-5'-phosphate decarboxylase (OPRT/ODCase), encoded by the UMPS gene in humans. The bifunctional enzyme catalyzes both the formation of OMP and its subsequent decarboxylation to UMP, linking de novo synthesis to nucleotide salvage.

Biochemically, OPRT requires divalent metal ions such as Mg2+ or Mn2+ and interacts with substrates PRPP and orotate. The produced OMP is commonly processed further by ODCase to yield UMP. Beyond its role in metabolism, OPRT can also activate certain anticancer and antiviral drugs, such as 5-fluorouracil, which is ribosylated to 5-fluorouridine monophosphate by OPRT.

Clinical relevance includes UMPS deficiency, which can cause orotic aciduria and related metabolic abnormalities. OPRT continues to be studied as a potential antimicrobial and anticancer drug target, as well as a key enzyme in pyrimidine metabolism.