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Item Type: | Article |
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Title: | Decoding the dynamics of cellular metabolism and the action of 3-bromopyruvate and 2-deoxyglucose using pulsed stable isotope-resolved metabolomics |
Creators Name: | Pietzke, M., Zasada, C., Mudrich, S. and Kempa, S. |
Abstract: | BACKGROUND: Cellular metabolism is highly dynamic and continuously adjusts to the physiological program of the cell. The regulation of metabolism appears at all biological levels: (post-) transcriptional, (post-) translational, and allosteric. This regulatory information is expressed in the metabolome, but in a complex manner. To decode such complex information, new methods are needed in order to facilitate dynamic metabolic characterization at high resolution. RESULTS: Here, we describe pulsed stable isotope-resolved metabolomics (pSIRM) as a tool for the dynamic metabolic characterization of cellular metabolism. We have adapted gas chromatography-coupled mass spectrometric methods for metabolomic profiling and stable isotope-resolved metabolomics. In addition, we have improved robustness and reproducibility and implemented a strategy for the absolute quantification of metabolites. CONCLUSIONS: By way of examples, we have applied this methodology to characterize central carbon metabolism of a panel of cancer cell lines and to determine the mode of metabolic inhibition of glycolytic inhibitors in times ranging from minutes to hours. Using pSIRM, we observed that 2-deoxyglucose is a metabolic inhibitor, but does not directly act on the glycolytic cascade. |
Keywords: | Stable Isotope Labeling, GC-MS, Cancer Metabolism, Glycolysis, Metabolomics, 3-Bromopyruvate, 2-Deoxyglucose |
Source: | Cancer & Metabolism |
ISSN: | 2049-3002 |
Publisher: | BioMed Central |
Volume: | 2 |
Page Range: | 9 |
Date: | 30 June 2014 |
Official Publication: | https://doi.org/10.1186/2049-3002-2-9 |
PubMed: | View item in PubMed |
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