Uridine monophosphate synthase (UMPS)

Uridine monophosphate synthase (UMPS) is a bifunctional enzyme that catalyzes the last two steps of the de novo biosynthesis of pyrimidines, specifically converting orotate to uridine monophosphate (UMP) via orotate phosphoribosyltransferase (OPRTase, N-terminal domain) and orotidine-5'-phosphate decarboxylase (ODCase/C-terminal domain) activities[1][2][3][4]. UMPS is essential for nucleotide metabolism in all dividing cells, and mutations leading to loss of function result in the rare disorder hereditary orotic aciduria, characterized by elevated urinary orotic acid, developmental delay, and megaloblastic anemia. The enzyme is a therapeutic target in the sense that deficiencies cause metabolic disease; its individual enzymatic domains can be individually targeted in biochemical research, though no approved drugs directly target UMPS in clinical practice[1][2][4].

Other names

orotate phosphoribosyltransferase and orotidine-5'-decarboxylaseorotidine 5'-phosphate decarboxylaseUMP synthaseorotate phosphoribosyl transferase and orotidine-5'-phosphate decarboxylase

Enzyme inhibition (inhibitors block the catalytic activities of either or both the orotate phosphoribosyltransferase or orotidine-5’-phosphate decarboxylase domains)[4]