Department of Medicinal Chemistry, Science for Life Laboratory, Uppsala University, Box 574, 75123, Uppsala, Sweden.
Chembiochem. 2019 Jul 1;20(13):1678-1683. doi: 10.1002/cbic.201900065. Epub 2019 May 8.
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.
糖基化是最常见的 II 期修饰，在人体清除代谢中起着重要作用。糖基化代谢物也与疾病发展和微生物群-宿主共代谢有关。尽管已经鉴定出许多这些化合物，但未知糖基化物的总数及其对人体宿主生理学的影响只能估计。在这里，我们描述了一种非靶向代谢组学分析和酶代谢转化的组合，用于通过 UPLC-MS/MS 在人尿样中选择性检测糖基化缀合物。我们的研究表明，这种强大的策略可用于选择性鉴定糖基化分子，并发现未知的天然代谢物。在一个单独的样本中，我们总共鉴定出 191 种代谢物，包括微生物群衍生的化合物和以前未鉴定的分子。
