Superoxide-dependent Oxidation of Melatonin by

Myeloperoxidase uses hydrogen peroxide to oxidize numerous substrates to hypohalous acids or reactive free radicals. Here we show that neutrophils oxidize melatonin toN1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) in a reaction that is catalyzed by myeloperoxidase. Production of AFMK was highly dependent on superoxide but not hydrogen peroxide. It did not require hypochlo-rous acid, singlet oxygen, or hydroxyl radical. Purifiedmyeloperoxi-dase and a superoxide-generating system oxidized melatonin to AFMK and a dimer. The dimer would result from coupling of mela-tonin radicals. Oxidation of melatonin was partially inhibited by catalase or superoxide dismutase. Formation of AFMK was almost completely eliminated by superoxide dismutase but weakly inhib-ited by catalase. In contrast, production of melatonin dimer was enhanced by superoxide dismutase and blocked by catalase. We propose thatmyeloperoxidase uses superoxide to oxidizemelatoni