The significance of the metabolism of the neurohormone melatonin: Antioxidative protection and formation of bioactive substances

Recent findings suggest that the ability of melatonin to enter all body tissues and to be metabolized, enzymatically or nonenzymatically, in any of them results in a spectrum of effects, which exceed substantially those transduced by membrane receptors. These actions comprise the formation of various bioactive compounds such as N-acetylserotonin, 5-methoxytryptamine, N,N-dimethyl-5-methoxytryptamine, 5-methoxytrytophol, cyclic 2-hydroxymelatonin, pinoline, and 5-methoxylated kynuramines. Apart from enzymatic metabolism, nonenzymatic reactions with free radicals, in particular the superoxide anion and the hydroxyl radical, represent a new and significant aspect of melatonin's biological role. Melatonin represents the most potent physiological scavenger of hydroxyl radicals found to date, and recent findings suggest an essential role of this indoleamine for protection from hydroxyl radical-induced carcinogenesis and neurodegeneration.