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.
- Free radical
- Hydrogen peroxide
- N-acetyl-N -formyl-5-methoxykynuramine
ASJC Scopus subject areas
- Physiology (medical)