Uracil phosphoribosyltransferase (UPRTase)

Uracil phosphoribosyltransferase is an enzyme that catalyzes the conversion of uracil and 5-phospho-α-D-ribose 1-diphosphate (PRPP) into uridine 5′-monophosphate (UMP) and pyrophosphate, a key reaction in the pyrimidine salvage pathway[1][4][8]. This enzyme is highly specific for uracil and cannot utilize cytosine, cytidine, deoxycytidine, or thymine due to steric constraints in the active site[1][5]. UPRTase has a conserved PRPP-binding motif and is a member of the phosphoribosyltransferase family[3][5]. In some pathogenic organisms (e.g., Toxoplasma gondii, Mycobacterium tuberculosis), it is considered a rational drug target for antiparasitic or antibacterial therapy, while in humans, UMP synthesis is also achieved via alternative pathways involving uridine phosphorylase and uridine kinase[5]. Inhibition or genetic disruption of UPRTase in pathogens can cause nucleotide starvation and cell death, but targeting human UPRTase could interfere with normal pyrimidine metabolism and viability[6].

Other names

UPRTaseUPRTuracil phosphoribosyltransferase (upp in many bacteria)UPP

Catalyzes the transfer of a ribosyl phosphate group from α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) to uracil, forming UMP and inorganic pyrophosphate (PPi)[1][4][8]. In organisms where the enzyme activates 5-fluorouracil, it is involved in prodrug activation leading to nucleotide antimetabolite cytotoxicity.