Bridging the gap between non-targeted stable isotope labeling and metabolic flux analysis
| Autor: | Xiangyi Dong, Sean C. Sapcariu, Andre Wegner, Karsten Hiller, Daniel Weindl, Thekla Cordes, Nadia Battello |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Non-targeted Methodology Context (language use) Computational biology Metabolism Biology Glutamine 03 medical and health sciences Psychiatry and Mental health N-acetylaspartate 030104 developmental biology Metabolomics Biochemistry NAT8L Metabolic flux analysis Cancer cell Gene silencing Mass isotopomer distribution analysis NTFD Stable isotope labeling Flux (metabolism) Flux analysis Cancer |
| Zdroj: | Cancer & Metabolism |
| ISSN: | 2049-3002 |
| DOI: | 10.1186/s40170-016-0150-z |
| Popis: | Background Metabolism gained increasing interest for the understanding of diseases and to pinpoint therapeutic intervention points. However, classical metabolomics techniques only provide a very static view on metabolism. Metabolic flux analysis methods, on the other hand, are highly targeted and require detailed knowledge on metabolism beforehand. Results We present a novel workflow to analyze non-targeted metabolome-wide stable isotope labeling data to detect metabolic flux changes in a non-targeted manner. Furthermore, we show how similarity-analysis of isotopic enrichment patterns can be used for pathway contextualization of unidentified compounds. We illustrate our approach with the analysis of changes in cellular metabolism of human adenocarcinoma cells in response to decreased oxygen availability. Starting without a priori knowledge, we detect metabolic flux changes, leading to an increased glutamine contribution to acetyl-CoA production, reveal biosynthesis of N-acetylaspartate by N-acetyltransferase 8-like (NAT8L) in lung cancer cells and show that NAT8L silencing inhibits proliferation of A549, JHH-4, PH5CH8, and BEAS-2B cells. Conclusions Differential stable isotope labeling analysis provides qualitative metabolic flux information in a non-targeted manner. Furthermore, similarity analysis of enrichment patterns provides information on metabolically closely related compounds. N-acetylaspartate and NAT8L are important players in cancer cell metabolism, a context in which they have not received much attention yet. Electronic supplementary material The online version of this article (doi:10.1186/s40170-016-0150-z) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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