Xanthine dehydrogenase (XDH) (XO)

Xanthine dehydrogenase (XDH) is a molybdenum-containing enzyme that serves as a key component of the xanthine oxidoreductase system, primarily responsible for the final stages of purine catabolism (UniProt P47989). It catalyzes the oxidation of hypoxanthine to xanthine and subsequently xanthine to uric acid, a process that also generates reactive oxygen species (ROS) such as superoxide radicals (StatPearls, 2023). Elevated levels of uric acid resulting from XDH activity can lead to hyperuricemia and the development of gouty arthritis and renal calculi (NIH, 2022). In the context of pharmacology, XDH is a major therapeutic target for xanthine oxidase inhibitors like allopurinol and febuxostat, which are used to lower systemic urate levels. Additionally, XDH is involved in the metabolism of certain drugs; for instance, it oxidizes methotrexate into its metabolite 7-hydroxymethotrexate, which has lower solubility and can contribute to methotrexate-induced nephrotoxicity (PubMed, 5016640). Inhibition of this enzyme is also critical when administering thiopurines, as XDH is responsible for their inactivation, and its inhibition can lead to life-threatening myelosuppression.

Other names

Xanthine oxidoreductaseXORXanthine oxidaseHypoxanthine oxidase

Inhibition of the enzyme's catalytic activity to reduce the production of uric acid and reactive oxygen species.