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Coupled Enzymatic Treatment and Mass Spectrometric Analysis for Identification of Glucuronidated Metabolites in Human Samples
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Chemical Biology for Biomarker Discovery.ORCID iD: 0000-0003-2125-4184
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Chemical Biology for Biomarker Discovery.ORCID iD: 0000-0002-3059-9013
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Chemical Biology for Biomarker Discovery. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-4526-5788
2019 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 20, no 13, p. 1678-1683Article in journal (Refereed) Published
Abstract [en]

Glucuronidation is the most common phase II modification and plays an important role in human clearance metabolism. Glucuronidated metabolites have also been linked to disease development and microbiota-host co-metabolism. Although many of these compounds have been identified, the total number of unknown glucuronides and their impact on the human host's physiology can only be estimated. Herein, we describe the combination of an untargeted metabolomics analysis and enzymatic metabolic conversion for the selective detection of glucuronide conjugates by using UPLC-MS/MS in human urine samples. Our study demonstrates that this powerful strategy can be used for the selective identification of glucuronidated molecules and to discover unknown natural metabolites. In total, we identified 191 metabolites in a single sample including microbiota-derived compounds as well as previously unidentified molecules.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH , 2019. Vol. 20, no 13, p. 1678-1683
Keywords [en]
glucuronidase, mass spectrometry, metabolomics, microbiota, urine samples
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-392591DOI: 10.1002/cbic.201900065ISI: 000477916100010PubMedID: 30803115OAI: oai:DiVA.org:uu-392591DiVA, id: diva2:1349176
Funder
Swedish Research Council, 2016-04423Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceAvailable from: 2019-09-06 Created: 2019-09-06 Last updated: 2019-09-06Bibliographically approved

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Correia, Mario S. P.Ballet, CarolineGlobisch, Daniel

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Science for Life Laboratory, SciLifeLabChemical Biology for Biomarker DiscoveryDepartment of Medicinal Chemistry
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