orotatPRPPreaktion

The orotate phosphoribosyltransferase reaction, sometimes written as the orotate-PRPP reaction, is a key step in de novo pyrimidine biosynthesis. It transfers the ribose-phosphate moiety from 5-phosphoribosyl-1-pyrophosphate (PRPP) to orotate, forming orotidine-5′-phosphate (OMP) and releasing inorganic pyrophosphate (PPi).

In chemical terms, orotate plus PRPP yields OMP and PPi. This reaction is catalyzed by the enzyme orotate phosphoribosyltransferase (OPRT; EC 2.4.2.10). The transfer involves forming a glycosidic bond between the orotate nitrogen and the ribose moiety of PRPP. In many organisms, OPRT is encoded by a pyrE gene; in higher eukaryotes the OPRT activity is often part of a bifunctional enzyme that also carries orotidine-5′-phosphate decarboxylase (ODCase) activity, together functioning as UMPS.

Context within the pathway: the OMP produced by this reaction is subsequently decarboxylated to UMP by ODCase, completing the conversion of orotate to uridine monophosphate. The availability of PRPP and the active pool of pyrimidine nucleotides help regulate flux through this pathway. The reaction is essential for the synthesis of pyrimidine nucleotides used in RNA and DNA.

Clinical and biological relevance: defects in enzymes of this pathway, including OPRT or the bifunctional UMPS, can lead to metabolic disorders such as orotic aciduria, characterized by elevated orotic acid in urine and impaired nucleotide biosynthesis. The reaction is also a target for antimicrobial and anticancer strategies that aim to disrupt pyrimidine salvage and de novo synthesis.