Department of Neurosurgery, Henan People's Hospital, Zhengzhou, China.
J Pineal Res. 2013 Jan;54(1):100-6. doi: 10.1111/jpi.12003.
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.
外源性褪黑素被广泛应用于人类，具有多种药理学作用。褪黑素的代谢途径反映了褪黑素在体内的命运和功能。本研究旨在采用代谢组学方法重新分析人类褪黑素的代谢。在接受 10mg 褪黑素治疗的健康受试者的尿液中，检测到褪黑素的硫酸酯或葡萄糖醛酸缀合物代谢物，包括 6-羟褪黑素硫酸酯、6-羟褪黑素葡萄糖醛酸苷、N-乙酰色氨酸葡萄糖醛酸苷、N-乙酰色氨酸硫酸酯和一种未知的硫酸化代谢物 (X)。代谢物 X 的分子量比 6-羟褪黑素硫酸酯小 14Da，但比 N-乙酰色氨酸硫酸酯大 16Da。进一步的研究表明，代谢物 X 是通过 O-去甲基化、6-羟化和硫酸化生成的。褪黑素的抗氧化产物 N(1)-乙酰-N(2)-甲酰-5-甲氧基犬尿氨酸和 N(1)-乙酰-5-甲氧基犬尿氨酸未在人尿中检测到。总之，本研究提供了人类褪黑素代谢的全面视图，并扩展了我们对依赖酶的褪黑素代谢途径的认识。
