人类血浆、粪便和脑脊液样本中葡萄糖醛酸苷的全球代谢组学分析

IF 3.8 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS
Ioanna Tsiara, Mario S P Correia, Fan Yang, Weiming Zeng, Pauline Seeburger, Belén Hervás Povo, Iben Lundgaard, Manuel Menéndez-González, Miroslav Vujasinovic, J-Matthias Löhr, Daniel Globisch
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引用次数: 0

摘要

葡萄糖醛酸化是促进人体清除外源化合物的主要II期生物转化反应。葡萄糖醛酸化代谢物已经在尿液样本中进行了广泛的研究;然而,它们在其他人类生物标本中的表征尚未得到充分探索。我们的研究现已对人类血浆、粪便和脑脊液(CSF)中的葡萄糖醛酸酯进行了全面的分析。我们进行了基于质谱的分析,结合酶水解和β-葡萄糖醛酸酶选择性地切割葡萄糖醛酸部分,开发了内部葡萄糖醛酸鉴定管道,以及酶合成标准代谢物。利用先进的MS/MS碎片化分析,我们在阴性和阳性质谱电离模式下鉴定了三种样品类型中的32种糖醛酸化代谢物。我们在最高的置信水平上使用了葡萄糖醛酸化代谢物的直接酶合成。在鉴定的缀合物中,我们检测了不同化合物类别的葡萄糖醛酸酯,包括药物,胆汁酸衍生物,类固醇缀合物和酚类化合物。出乎意料的是,我们在脑脊液样本中验证了对乙酰氨基酚和异丙酚的葡萄糖醛酸盐,后者代表了一种新的观察结果,强调了在不常见的样品类型中研究II期代谢物的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Global metabolomics profiling of glucuronides in human plasma, fecal, and cerebrospinal fluid samples.

Glucuronidation is the major phase II biotransformation reaction that facilitates the clearance of exogenous compounds from the human body. Glucuronidated metabolites have been investigated in urine samples at a broad scale; however, their characterization in other human biospecimens is underexplored. Our study has now performed a comprehensive profiling of glucuronides in plasma, fecal, and cerebrospinal fluid (CSF) of humans. We performed a mass spectrometry-based analysis that combines enzymatic hydrolysis with a β-glucuronidase to selectively cleave the glucuronic acid moiety, a developed in-house glucuronide identification pipeline, and enzymatic synthesis of standard metabolites. In total, we identified 32 glucuronidated metabolites across the three sample types in both negative and positive mass spectrometry ionization modes using advanced MS/MS fragmentation analysis. We have utilized a straightforward enzymatic synthesis of glucuronidated metabolites for annotation at the highest confidence level. Among the identified conjugates, we detected glucuronides of different compound classes including drugs, bile acid derivatives, steroid conjugates, and phenolic compounds. Unexpectedly, we validated the glucuronides of acetaminophen and propofol in CSF samples, the latter representing a novel observation that highlights the importance of investigating phase II metabolites in uncommon sample types.

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来源期刊
CiteScore
8.00
自引率
4.70%
发文量
638
审稿时长
2.1 months
期刊介绍: Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.
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