摘要：Xanthine oxidase (XO)/xanthine dehydrogenase (XD) oxidizes oxypurines to uric acid, with only the XO form producing reactive oxygen species. In the present study, the effects of cystamine S -monoxide and cystine S -monoxide (disulfide S -monoxides) on the conversion of XD to XO in rat liver were examined. A partially purified enzyme fraction from the rat liver was incubated with xanthine in the presence or absence of NAD+, and the uric acid formed was measured by HPLC. Under basal conditions, XO activity represented about 15% of the total XO plus XD activity. Cystamine S -monoxide and cystine S -monoxide converted XD into XO in a dose-dependent manner, and the concentrations required to increase XO activity by 50% were approximately 1 and 2 μ M , respectively. Their respective thiols (cysteamine and cysteine) and disulfides (cystamine and cystine) up to 10 μ M showed weak or no effects on the activities of XO and XD and their conversion. Experiments utilizing a sulfhydryl reducing reagent (dithiothreitol) and sulfhydryl modifiers (4,4′-dithiodipyridine and 1-fluoro-2,4-dinitrobenzene) indicated that disulfide S -monoxides-induced conversion of XD to XO occurs via disulfide bridge formation in XD, but not the modification of sulfhydryl groups. These results suggest that disulfide S -monoxides have the potential to increase the generation of reactive oxygen species through the conversion of XD to XO in liver.
