Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells
Altered central carbon metabolism is a hallmark of many diseases including diabetes, obesity, heart disease and cancer. Identifying metabolic changes will open opportunities for better understanding aetiological processes and identifying new diagnostic, prognostic, and therapeutic targets. Comprehen...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2020
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| _version_ | 1797083274502209536 |
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| author | Walsby-Tickle, J Gannon, J Hvinden, I Bardella, C Abboud, MI Nazeer, A Hauton, D Pires, E Cadoux-Hudson, T Schofield, CJ McCullagh, JSO |
| author_facet | Walsby-Tickle, J Gannon, J Hvinden, I Bardella, C Abboud, MI Nazeer, A Hauton, D Pires, E Cadoux-Hudson, T Schofield, CJ McCullagh, JSO |
| author_sort | Walsby-Tickle, J |
| collection | OXFORD |
| description | Altered central carbon metabolism is a hallmark of many diseases including diabetes, obesity, heart disease and cancer. Identifying metabolic changes will open opportunities for better understanding aetiological processes and identifying new diagnostic, prognostic, and therapeutic targets. Comprehensive and robust analysis of primary metabolic pathways in cells, tissues and bio-fluids, remains technically challenging. We report on the development and validation of a highly reproducible and robust untargeted method using anion-exchange tandem mass spectrometry (IC-MS) that enables analysis of 431 metabolites, providing detailed coverage of central carbon metabolism. We apply the method in an untargeted, discovery-driven workflow to investigate the metabolic effects of isocitrate dehydrogenase 1 (IDH1) mutations in glioblastoma cells. IC-MS provides comprehensive coverage of central metabolic pathways revealing significant elevation of 2-hydroxyglutarate and depletion of 2-oxoglutarate. Further analysis of the data reveals depletion in additional metabolites including previously unrecognised changes in lysine and tryptophan metabolism. |
| first_indexed | 2024-03-07T01:39:25Z |
| format | Journal article |
| id | oxford-uuid:965770ad-4607-4763-897f-45930c57dd7f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:39:25Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:965770ad-4607-4763-897f-45930c57dd7f2022-03-26T23:52:19ZAnion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:965770ad-4607-4763-897f-45930c57dd7fEnglishSymplectic ElementsSpringer Nature2020Walsby-Tickle, JGannon, JHvinden, IBardella, CAbboud, MINazeer, AHauton, DPires, ECadoux-Hudson, TSchofield, CJMcCullagh, JSOAltered central carbon metabolism is a hallmark of many diseases including diabetes, obesity, heart disease and cancer. Identifying metabolic changes will open opportunities for better understanding aetiological processes and identifying new diagnostic, prognostic, and therapeutic targets. Comprehensive and robust analysis of primary metabolic pathways in cells, tissues and bio-fluids, remains technically challenging. We report on the development and validation of a highly reproducible and robust untargeted method using anion-exchange tandem mass spectrometry (IC-MS) that enables analysis of 431 metabolites, providing detailed coverage of central carbon metabolism. We apply the method in an untargeted, discovery-driven workflow to investigate the metabolic effects of isocitrate dehydrogenase 1 (IDH1) mutations in glioblastoma cells. IC-MS provides comprehensive coverage of central metabolic pathways revealing significant elevation of 2-hydroxyglutarate and depletion of 2-oxoglutarate. Further analysis of the data reveals depletion in additional metabolites including previously unrecognised changes in lysine and tryptophan metabolism. |
| spellingShingle | Walsby-Tickle, J Gannon, J Hvinden, I Bardella, C Abboud, MI Nazeer, A Hauton, D Pires, E Cadoux-Hudson, T Schofield, CJ McCullagh, JSO Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells |
| title | Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells |
| title_full | Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells |
| title_fullStr | Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells |
| title_full_unstemmed | Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells |
| title_short | Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells |
| title_sort | anion exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in idh1 mutant cells |
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