Melatonin directly scavenges hydrogen peroxide: A potentially new metabolic pathway of melatonin biotransformation

A potential new metabolic pathway of melatonin biotransformation is described in this investigation. Melatonin was found to directly scavenge hydrogen peroxide (H₂O₂) to form N¹-acetyl-N²-formyl-5-methoxykynuramine and, thereafter this compound could be enzymatically converted to N¹-acetyl-5-methoxykynuramine by catalase. The structures of these kynuramines were identified using proton nuclear magnetic resonance, carbon nuclear magnetic resonance, and mass spectrometry. This is the first report to reveal a possible physiological association between melatonin, H₂O₂, catalase, and kynuramines. Melatonin scavenges H₂O₂ in a concentration-dependent manner. This reaction appears to exhibit two distinguishable phases. In the rapid reaction phase, the interaction between melatonin and H₂O₂ reaches equilibrium rapidly (within 5 s). The rate constant for this phase was calculated to be 2.3 x 10⁶ M^-1s^-1. Thereafter, the relative equilibrium of melatonin and H₂O₂ was sustained for roughly 1 h, at which time the content of H₂O₂ decreased gradually over a several hour period, identified as the slow reaction phase. These observations suggest that melatonin, a ubiquitously distributed small nonenzymatic molecule, might serve to directly detoxify H₂O₂ in living organisms. H₂O₂ and melatonin are present in all subcellular compartments; thus, presumably, one important function of melatonin may be complementary in function to catalase and glutathione peroxidase in keeping intracellular H₂O₂ concentrations at steady-state levels. Copyright (C) 2000 Elsevier Science Inc.