Metabolism of melatonin by cytochrome P450s in rat liver mitochondria and microsomes.

Journal of Pineal Research
Igor SemakAndrzej Slominski

Abstract

In the present study we provide direct evidence for the involvement of rat microsomal cytochrome P450s in melatonin O-demethylation and hydroxylation at two different positions: 2 and 6, as well as generation of N(1)-acetyl-N(2)-formyl-5-methoxy-kynuramine (AFMK) and two unknown products. Moreover, we found that mitochondrial cytochrome P450s also converts melatonin into AFMK, N-acetylserotonin, 2-hydroxymelatonin, 6-hydroxymelatonin and the same two unknown products. Eadie-Hofstee plots for 6-hydroxylation and O-demethylation reactions were curvilinear for all tested fractions, suggestive of involvement of at least two components, one with a high affinity and low capacity, and another with a low affinity and high capacity. Mitochondrial cytochrome P450s exhibited higher affinity (suggesting lower K(m) value) and higher V(max) for melatonin 6-hydroxylation and O-demethylation for both high-affinity and low-affinity components as compared with microsomal enzymes. The intrinsic clearance for melatonin hydroxylation by high- and low-affinity components displayed the highest values in all tested fractions, indicating that both mitochondrial and microsomal cytochrome P450s metabolize melatonin principally by 6-hydroxylation, with O-...Continue Reading

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Citations

Dec 31, 2009·Biological Reviews of the Cambridge Philosophical Society·Dun-Xian TanRussel J Reiter
Mar 27, 2010·Arhiv za higijenu rada i toksikologiju·Seema Sharma, Suresh Vir Singh Rana
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Jul 19, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhou-Yue WuFeng Han
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