Xanthine oxidoreductase mediates the successive oxidation of hypoxanthine and xanthine to produce uric acid. The enzyme can interconvert between xanthine dehydrogenase and xanthine oxidase activities through reversible sulfhydryl oxidation on specific cysteine residues. Both forms oxidize hypoxanthine and xanthine to uric acid. However the dehydrogenase simultaneously reduces nicotinamide adenine dinucleotide while the oxidase reduces oxygen to superoxide. Allopurinol is an isomer of hypoxanthine that inhibits xanthine oxidoreductase (IC50 values between 0.2 and 50 μM, depending on assay and cell type).1,2In vivo, allopurinol has been reported to effectively and safely lower serum and urinary uric acid levels and is also reported to be effective in the treatment of gout and hyperuricemia. Allopurinol is rapidly metabolized in vivo to the xanthine analog oxypurinol, which is a metabolite that clearly augments the therapeutic effect of allopurinol.3
1
Fujimoto, Y., Sakuma, S., Tagami, T., et al. N-ethylmaleimide inhibits xanthine oxidase activity with no detectable change in xanthine dehydrogenase activity in rabbit liver. Life Sci68517-524(2000).
2
Pacher, P., Nivorozhkin, A., and Szabó, C. Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol. Pharmacol Rev58(1)87-114(2006).
3
Day, R.O., Graham, G.G., Hicks, M., et al. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet46(8)623-644(2007).