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(2)O(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(2)O(2), catalase, and kynuramines. Melatonin scavenges H(2)O(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(2)O(2) reaches equilibrium rapidly (within 5 s). The rate constant for this phase was calculated to be 2.3 x 10(6) M(-1)s(-1). Thereafter, the relative equilibrium of melatonin and H(2)O(2) was sustained for roughly 1 h, at which time the content of H(2)O(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(2)O(2) in living organisms. H(2)O(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(2)O(2) concentrations at steady-state levels.
Tan
D X
DX
Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Manchester
L C
LC
Reiter
R J
RJ
Plummer
B F
BF
Limson
J
J
Weintraub
S T
ST
Qi
W
W
D002374:Catalase / Q000378:metabolism; D016166:Free Radical Scavengers; D005979:Glutathione Peroxidase; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism; D007700:Kinetics; D007735:Kynuramine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008550:Melatonin / Q000378:metabolism*
D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D007735:Kynuramine; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D008550:Melatonin