Fig. 6

Schematic review of the hypothesis. When an organ is exposed to anaerobic condition, high-energy phosphates are degraded, and accumulation of xanthine and uric acid are usually greater than hypoxanthine in tissues through conversion of hypoxanthine to xanthine, and xanthine to uric acid by XDH activity. After reperfusion, these purine metabolites are washed out from tissues without XOR inhibition. Meanwhile, administration of non-purine-XOR inhibitors induce hypoxanthine accumulation in tissues by inhibiting XDH. After reperfusion, this excessive hypoxanthine is converted to IMP by hypoxanthine-guanine phosphoribosyltransferase (HGPRTase), a salvage pathway enzyme, which will be utilized for ATP resynthesis, and thus contribute to better energetic outcomes. As allopurinol itself act as a substrate for HGPRTase consuming PRPP, administration of allopurinol may inhibit ATP resynthesis via the salvage pathway. PRPP, phosphoribosyl diphosphate; ATP, adenosine triphosphate; ADP, adenosine diphosphate; AMP, adenosine 5′-monophosphate; IMP, inosine monophosphate; XOR, xanthine oxidoreductase