NADPH-dependent flavoenzymes catalyze one electron reduction of metal ions and molecular oxygen and generate hydroxyl radicals

This study reports a new property of the important NAD(P)H-dependent flavoenzymes, glutathione reductase, lipoyl dehydrogenase and ferredoxin-NADP⁺ oxidoreductase, that can catalyze a one electron reduction of metal ions such as chromium(VI) and vanadium(V). During the enzymatic reduction process, molecular oxygen is reduced to H₂O₂, which reacts with the reduced metal complexes to generate hydroxyl radicals. Since the hydroxyl radicals have been suggested to play an important role in Cr(VI) toxicity, this study provides a basis for a recent observation that Cr(VI) mutagenesis is strongly oxygen dependent. These results also point to an enzymatic pathway for the metabolism of some metal ions and concomitant generation of hydroxyl radicals.