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Comprehensive Profiling by Non-targeted Stable Isotope Tracing Capillary Electrophoresis-Mass Spectrometry: A New Tool Complementing Metabolomic Analyses of Polar Metabolites
Authors:Dr Jun Zeng  Dr Zhichao Wang  Dr Xin Huang  Dr Sabine S Eckstein  Prof?Dr Xiaohui Lin  Prof?Dr Hailong Piao  Prof?Dr Cora Weigert  Dr Peiyuan Yin  Prof?Dr Rainer Lehmann  Prof?Dr Guowang Xu
Affiliation:1. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023 China;2. Department of Computer Science & Engineering, Dalian University of Technology, Dalian, 116024 China;3. Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, Germany

Core Facility German Center for Diabetes Research (DZD), Clinical Chemistry Laboratory, Institute for Diabetes Research and Metabolic Diseases, University Hospital Tübingen, 72076 Tübingen, Germany

German Center for Diabetes Research (DZD), Tübingen, Germany;4. Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, Germany

Abstract:Mass spectrometry (MS) driven metabolomics is a frequently used tool in various areas of life sciences; however, the analysis of polar metabolites is less commonly included. In general, metabolomic analyses lead to the detection of the total amount of all covered metabolites. This is currently a major limitation with respect to metabolites showing high turnover rates, but no changes in their concentration. Such metabolites and pathways could be crucial metabolic nodes (e.g., potential drug targets in cancer metabolism). A stable-isotope tracing capillary electrophoresis–mass spectrometry (CE-MS) metabolomic approach was developed to cover both polar metabolites and isotopologues in a non-targeted way. An in-house developed software enables high throughput processing of complex multidimensional data. The practicability is demonstrated analyzing U-13C]-glucose exposed prostate cancer and non-cancer cells. This CE-MS-driven analytical strategy complements polar metabolite profiles through isotopologue labeling patterns, thereby improving not only the metabolomic coverage, but also the understanding of metabolism.
Keywords:capillary electrophoresis  isotopologues  mass spectrometry  metabolism  metabolomics
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