A Novel Metabolic Pathway of Melatonin: Oxidation by Cytochrome c

详细信息    查看全文

• 作者：Igor Semak ; Marya Naumova ; Elena Korik ; Victorya Terekhovich ; Jacobo Wortsman ; and Andrzej Slominski
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：July 5, 2005
• 年：2005
• 卷：44
• 期：26
• 页码：9300 - 9307
• 全文大小：191K
• 年卷期：v.44,no.26(July 5, 2005)
• ISSN：1520-4995

文摘

The indoleamine melatonin is ubiquitously distributed, and because of its small size andamphiphilic nature, it is able to reach easily all cellular compartments. The highest intracellular melatoninconcentrations are found in the mitochondria, suggestive of local metabolism and/or direct participationin organelle function. In mitochondria cytochrome c (cyt c) could represent a melatonin target since it hasthe capability to oxidize organic molecules in the presence of H₂O₂, and mitochondria are the main siteof H₂O₂ production in nonphagocytic cells. Therefore, we investigated oxidation of melatonin by cytc/H₂O₂ couple as a potential pathway for its metabolism in the mitochondria. We found melatoninconversion into N¹-acetyl-N²-formyl-5-methoxykynuramine via sequential steps that generate the intermediates 2-hydroxymelatonin and 2,3-dihydroxymelatonin. We experimentally excluded mediation by a Fenton/Haber-Weiss-type reaction and documented the dependence on oxoferryl heme for melatonin oxidation.Given the high mitochondrial concentrations of both melatonin and cyt c as well as the continuousgeneration of H₂O₂ during respiration, it is entirely possible that mitochondrial cyt c-mediated oxidationof melatonin may be a plausible pathway of its biotransformation in vivo.