A novel enzyme-dependent melatonin metabolite in humans
A novel enzyme-dependent melatonin metabolite in humans
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DOI：
10.1111/jpi.12003
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发表时间：
2013-01-01
影响因子：
10.3
通讯作者：
Ma, Xiaochao
中科院分区：
文献类型：
--
作者：
Li, Chaoyue;Li, Guangming;Ma, Xiaochao
外源性褪黑激素广泛用于人体多种药理学目的。褪黑素的代谢途径反映了褪黑素在体内的命运和功能。这项研究旨在利用代谢组学方法重新分析人类褪黑激素的代谢。在接受 10 mg 褪黑素治疗的健康受试者的尿液中，检测到褪黑素的硫酸盐或葡萄糖醛酸结合代谢物，包括硫酸 6-羟基褪黑素、6-羟基褪黑素葡萄糖醛酸、N-乙酰血清素葡萄糖醛酸、N-乙酰血清素硫酸盐和未知的硫酸化代谢物 (X)。代谢物X的分子量比6-羟基褪黑素硫酸盐小14Da，但比N-乙酰5-羟色胺硫酸盐大16Da。进一步的研究表明，代谢物 X 是通过 O-去甲基化、6-羟基化和硫酸化产生的。在人尿液中未检测到褪黑激素的抗氧化产物N(1)-乙酰基-N(2)-甲酰基-5-甲氧基犬尿明和N(1)-乙酰基-5-甲氧基-犬尿明。总之，这项研究提供了人类褪黑激素代谢的全局视图，并扩展了我们对褪黑激素代谢酶依赖性途径的了解。
Exogenous melatonin is widely used in humans for multiple pharmacologic purposes. The metabolic pathways of melatonin reflect the fate and functions of melatonin in vivo. This study was designed to re-profile melatonin metabolism in humans using a metabolomic approach. In the urine of healthy subjects treated with 10 mg melatonin, sulfate- or glucuronide-conjugated metabolites of melatonin were detected, including 6-hydroxymelatonin sulfate, 6-hydroxymelatonin glucuronide, N-acetylserotonin glucuronide, N-acetylserotonin sulfate, and an unknown sulfated metabolite (X). The molecular weight of metabolite X was 14 Da smaller than 6-hydroxymelatonin sulfate, but 16 Da larger than N-acetylserotonin sulfate. Further studies suggest that metabolite X was produced via O-demethylation, 6-hydroxylation, and sulfation. The antioxidant products of melatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxy-kynuramine, were not detected in human urine. In summary, this study provided a global view of melatonin metabolism in humans and extended our knowledge of enzyme-dependent pathways of melatonin metabolism.