Hydroxyl radical formation and iron-binding proteins. Stimulation by the purple acid phosphatases.

Abstract The effect of the purple acid phosphatases with binuclear iron centers (uteroferrin and bovine spleen phosphatase) on hydroxyl radical formation by iron-catalyzed Haber-Weiss-Fenton chemistry has been compared to that of lactoferrin and transferrin. Using 5,5-dimethyl-1-pyrroline-1-oxide to detect superoxide and hydroxyl radicals and the xanthine-xanthine oxidase system to generate superoxide and hydrogen peroxide, we have observed by ESR spectroscopy that both phosphatases were able to promote hydroxyl radical formation. Lactoferrin and transferrin were found incapable of giving rise to these reactive species. This can be explained by the fact that lactoferrin and transferrin carry two Fe(III) atoms per molecule, neither of which are readily reduced by biological reductants. In contrast, the phosphatases possess a binuclear iron center in which one of the iron atoms is stabilized in the ferric state, but the other freely undergoes one-electron redox reactions. The redox-active iron may act as a catalyst of the Haber-Weiss-Fenton sequence, thus enabling the reactions generating hydroxyl radical to proceed. The iron complex of diethylenetriamine penta-acetic acid, also redox active, was investigated and found as well to promote Haber-Weiss-Fenton chemistry.