Fig. 1.

Purine metabolism and oxidative stress. Purine metabolism involves the hydrolysis of phosphate molecules such as ATP and GTP into nucleosides such as adenine, inosine, and guanine. Briefly, ATP is conversed into ADP by ATPase, then into ADP by adenylate kinase. Next, AMP can be transformed into ADO or IMP by 5’-nucleotidase and AMP aminohydrolase, respectively. Both can be converted into inosine by adenosine deaminase or 5’-nucleotidase as well. Finally, inosine can be metabolized into hypoxanthine, a purine derivative that compounds the salvage pathway that controls purine metabolism. Adenine can be converted into hypoxanthine as well by the action of the adenine deaminase enzyme. Hypoxanthine can be transformed into xanthine by xanthine oxidoreductase. Finally, GTP can be converted into GDP, GMP, and guanosine by different nucleotidases. Then, guanosine can be metabolized by purine nucleoside phosphorylase, generating guanine directly converted into xanthine by guanine deaminase. The purine-based xanthine, by the action of the xanthine oxidoreductase, can be altered to uric acid, representing the final stage of this enzymatic conversions in humans, as they lack the uricase enzyme that converts uric acid in allantoin, present in animals such as mice and rats. Thus, uric acid can accumulate and crystalize in the joints of humans and causes various conditions such as gout due to hyperuricemia. It is noteworthy that xanthine oxidoreductase possesses enzymatic forms, xanthine oxidase, and xanthine dehydrogenase, that in addition to altering purine metabolites, act in redox biology, as the former may produce reactive oxygen species such as superoxide and hydrogen peroxide as by-products and the latter may present NADH oxidase properties and thus, reduces NAD⁺ into NADH, contributing to the pro-oxidant system as well.