Uridine phosphorylase 2 (UPP2)

Uridine phosphorylase 2 is an enzyme that catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate[3][5]. This activity is essential for pyrimidine salvage, nucleotide synthesis, and regulation of uridine concentrations in cells. UPP2 has substrate specificity for uridine, deoxyuridine, thymidine, and pyrimidine nucleoside analogs such as 5-fluorouridine. Unlike its homolog UPP1, UPP2 features a unique redox-sensitive regulatory mechanism: the formation of a reversible intramolecular disulfide bridge disrupts its active site, modulating its activity in response to cellular oxidative state[1][2]. UPP2 is implicated in the activation of fluoropyrimidine drugs (e.g., 5-FU and capecitabine) used in cancer therapy, and its inhibition can increase uridine concentrations, providing cytoprotection for non-cancerous cells during treatment. Emerging evidence suggests it may play additional roles in sensing oxidative stress and potentially regulating lipid metabolism[1][2]. UPP2 is a promising target in oncology and neuroprotection, though its broader physiological impact and therapeutic safety profile require further study.

Other names

UPase 2UrdPase 2UPASE2UP2UDRPASE2Liver-specific uridine phosphorylaseUridine phosphorylase 2

Enzymatic activation of fluoropyrimidine nucleoside drugs (conversion of prodrugs into cytotoxic metabolites) Inhibition of UPP2 (e.g., BAU) increases endogenous uridine concentration to protect normal cells from chemotherapeutic toxicity