Uridine 5'-monophosphate synthase (Orotate phosphoribosyltransferase domain) (UMPS)

Uridine 5'-monophosphate synthase (UMPS) is a bifunctional enzyme that plays a central role in the de novo pyrimidine biosynthetic pathway [1]. The enzyme contains two catalytic activities: orotate phosphoribosyltransferase (OPRT) and orotidine-5'-phosphate decarboxylase (ODCase) [2]. The OPRT domain specifically catalyzes the conversion of orotic acid and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) into orotidine 5'-monophosphate (OMP) [1]. This metabolic step is vital for cellular proliferation as it provides the building blocks for RNA and DNA synthesis [2]. Beyond its endogenous role, OPRT is the primary enzyme responsible for the metabolic activation of the anticancer drug 5-fluorouracil (5-FU) into its active nucleotide form, 5-fluorouridine monophosphate (FUMP) [3]. Consequently, OPRT expression levels are frequently studied as a predictive biomarker for the clinical response to 5-FU in various cancers, including colorectal and gastric malignancies [3]. Genetic deficiencies in this enzyme result in hereditary orotic aciduria, a condition marked by excessive urinary excretion of orotic acid and hematological abnormalities such as megaloblastic anemia [4].

Other names

Orotate phosphoribosyltransferaseOPRTOPRTaseOMP synthaseUridine 5'-monophosphate synthase

The OPRT domain catalyzes the conversion of orotate and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to orotidine 5'-monophosphate (OMP) [1][2]. In the context of chemotherapy, it acts as a prodrug activator by converting 5-fluorouracil (5-FU) into 5-fluorouridine monophosphate (FUMP), which is a necessary step for 5-FU's cytotoxic effects [3].