The influence of lipid peroxidation products (malondialdehyde, 4-hydroxynonenal) on xanthine oxidoreductase prepared from rat liver.

Depending on metabolic conditions, xanthine oxidoreductase acts as either a dehydrogenase (XDH) or an oxidase (XOD). The metabolism of hypoxanthine and xanthine by the oxidase is associated with the production of reactive oxygen radicals. Reaction of reactive oxygen radicals with polyunsaturated fatty acids (lipid peroxidation) leads to the formation of malondialdehyde (MDA) and 4-hydroxynonenal (HNE), known to modify proteins by reaction with NH2- and SH-groups. Therefore, these aldehydes could influence both the activity of xanthine oxidoreductase and the XOD/XDH ratio. We found that incubation of xanthine oxidoreductase with MDA leads to an initial increase in XDH activity and to a continuous decrease in XOD activity, whereby the total activity decreases. This was in contrast to the effects of HNE which did not alter the XDH activity; XOD was however activated. This demonstrates that the lipid peroxidation products MDA and HNE are able to modify xanthine oxidoreductase similarly to a feed-back mechanism.