Uridine monophosphate synthetase (UMPS) (UMPS)

Uridine monophosphate synthetase (UMPS) is a critical bifunctional human enzyme that plays a central role in the de novo pyrimidine biosynthetic pathway. It consists of two distinct catalytic domains: orotate phosphoribosyltransferase and orotidine-5'-phosphate decarboxylase, which sequentially transform orotic acid into uridine monophosphate (UMP), a precursor for all other pyrimidine nucleotides essential for DNA and RNA synthesis. Beyond its fundamental role in cellular metabolism, UMPS is a key pharmacological target due to its involvement in the metabolic activation of several fluoropyrimidine-based chemotherapeutic agents, such as 5-fluorouracil, which it converts into its active nucleotide form. Clinical interest in UMPS also stems from its link to hereditary orotic aciduria, a rare metabolic disorder where enzyme deficiency leads to megaloblastic anemia and growth impairment. Consequently, monitoring UMPS activity and expression is significant for diagnosing metabolic errors and predicting patient responses to specific anticancer treatments [16, 18].

Other names

Uridine 5'-monophosphate synthaseUMP synthaseOrotate phosphoribosyltransferase and orotidine-5'-decarboxylaseOPRTase/OMPdecaseOPRT/ODC

UMPS is a bifunctional enzyme that catalyzes the final two steps of de novo pyrimidine biosynthesis: the conversion of orotate and phosphoribosyl pyrophosphate (PRPP) into orotidine 5'-monophosphate (OMP) by its orotate phosphoribosyltransferase domain, followed by the decarboxylation of OMP to uridine 5'-monophosphate (UMP) by its orotidine-5'-phosphate decarboxylase domain. It also serves as a critical activating enzyme for the prodrug 5-fluorouracil (5-FU), converting it into 5-fluorouridine monophosphate (FUMP) [18].