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

A potential new metabolic pathway of melatonin biotransformation is describ ed in this investigation. Melatonin was found to directly scavenge hydrogen peroxide (H2O2) to form N-1-acetyl-N-2-formyl-5-methoxykynuramine and, the reafter this compound could be enzymatically converted to N-1-acetyl-5-meth oxykynuramine by catalase. The structures of these kynuramines were identif ied using proton nuclear magnetic resonance, carbon nuclear magnetic resona nce, and mass spectrometry. This is the first report to reveal a possible p hysiological association between melatonin, H2O2, catalase, and kynuramines . Melatonin scavenges H2O2 in a concentration-dependent manner. This reacti on appears to exhibit two distinguishable phases. In the rapid reaction pha se, 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 1 0(6) M(-1)s(-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 sma ll nonenzymatic molecule, might serve to directly detoxify H2O2 in living o rganisms. H2O2 and melatonin are present in all subcellular compartments; t hus, presumably, one important function of melatonin may be complementary i n function to catalase and glutathione peroxidase in keeping intracellular H2O2 concentrations at steady-state levels. (C) 2000 Elsevier Science Inc.