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 (H 2O 2) to form N 1-acetyl-N 2-formyl-5-methoxykynuramine and, thereafter this compound could be enzymatically converted to N 1-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, H 2O 2, catalase, and kynuramines. Melatonin scavenges H 2O 2 in a concentration-dependent manner. This reaction appears to exhibit two distinguishable phases. In the rapid reaction phase, the interaction between melatonin and H 2O 2 reaches equilibrium rapidly (within 5 s). The rate constant for this phase was calculated to be 2.3 × 10 6 M −1s −1. Thereafter, the relative equilibrium of melatonin and H 2O 2 was sustained for roughly 1 h, at which time the content of H 2O 2 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 H 2O 2 in living organisms. H 2O 2 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 H 2O 2 concentrations at steady-state levels.