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Xanthine oxidase (XO) is a molybdenum-containing enzyme that plays a pivotal role in the final stages of purine catabolism by catalyzing the oxidation of hypoxanthine to xanthine and xanthine to uric acid [UniProt P47989]. It is a key component of the xanthine oxidoreductase (XOR) system, which can interconvert between xanthine dehydrogenase (XDH) and XO forms [PubMed: 15662599]. The enzyme's substrate pocket, which houses the molybdenum cofactor (Mo-co), is the primary site for both substrate binding and pharmacological inhibition [PDB: 1FIQ]. Overproduction of uric acid by XO leads to hyperuricemia, the primary driver of gout and a contributor to renal calculi [StatPearls: Gout]. Additionally, XO is a major source of reactive oxygen species (ROS), contributing to oxidative stress in cardiovascular and inflammatory diseases [PubMed: 23532068]. Therapeutic agents like allopurinol and febuxostat target the substrate pocket; allopurinol acts as a suicide inhibitor after conversion to oxypurinol, while febuxostat provides potent, non-purine competitive inhibition [PubChem: CID 2090].
Inhibition of the molybdenum-containing active site (substrate pocket) to prevent the oxidation of hypoxanthine and xanthine into uric acid [StatPearls: Xanthine Oxidase Inhibitors].
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