The purine bases (adenine, guanine) components of nucleic acids (DNA, RNA) and ATP are metabolized to uric acid. In many mammals, uric acid is further degraded to allantoin by uricase, a urate oxidase, and excreted. On the other hand, in some primates, including humans, uric acid is the end product because uricase has been lost during evolution. The final step in purine metabolism, the hydroxylation of hypoxanthine to xanthine and xanthine to uric acid, is catalyzed by xanthine oxidoreductase (XOR). Uric acid production inhibitors exert their uric acid-lowering effects by inhibiting XOR. Allopurinol, febuxostat, and topiroxostat are currently used as XOR inhibitors. Each inhibitor differs in the presence or absence of a purine skeleton, mode of binding to the XOR, method of administration, and metabolic and excretory pathways. This difference can be attributed to the structure of the inhibitors. In particular, allopurinol is an analog of hypoxanthine, which is also known to be metabolized by other purine metabolizing enzymes. Oxypurinol, the major metabolite, has XOR inhibitory effects, but the details are unknown. We have studied the differences in inhibition mechanisms of each XOR inhibitor and found that the inhibitory effect on the step from hypoxanthine to xanthine is different. Hypoxanthine is recycled via the purine salvage pathway and has been shown to function in the inhibition of the purine de novo pathway and the maintenance of ATP. In this symposium, we will present the mechanism of inhibition of each XOR inhibitor and its effect on purine metabolism, including the data obtained from our studies.