Uridine phosphorylase 1 (UPP1)

Uridine phosphorylase 1 is a human enzyme encoded by the UPP1 gene that plays a central role in the pyrimidine salvage pathway by catalyzing the reversible phosphorolysis of uridine to uracil and ribose‑1‑phosphate. This reaction is crucial for both nucleotide synthesis and energy metabolism, as it allows cells to recycle pyrimidines for DNA/RNA synthesis or use them as carbon sources. UPP1 has broad substrate specificity, also acting on deoxyuridine and related compounds. UPP1 is clinically significant due to its involvement in activating fluoropyrimidine-based chemotherapeutic agents such as fluorouracil (5-FU) and capecitabine; these drugs rely on this enzyme for conversion into their active forms within tumor cells. Inhibitors targeting UPP1 can increase systemic uridine levels, which may protect normal tissues from chemotherapy-induced toxicity—a strategy under investigation for improving cancer treatment tolerability. Recent research suggests additional therapeutic potential for modulating UPP1 activity beyond oncology, including neuroprotection in ischemia or degenerative diseases like Alzheimer's or Parkinson's disease through regulation of cellular uridine concentrations. The enzyme’s structure reveals dynamic conformational changes during substrate binding that are relevant for drug design efforts aimed at developing more selective inhibitors with improved efficacy profiles.[1][2][3][10]

Other names

UPUPase 1UrdPase 1EC 2.4.2.3

Activation of prodrugs such as capecitabine to active cytotoxic metabolites in cancer therapy by catalyzing their conversion through the pyrimidine salvage pathway - Inhibition leads to increased endogenous uridine concentrations, providing cytoprotection against chemotherapeutic toxicity in normal tissues