Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
20 05 2020
20 05 2020
Historique:
received:
22
11
2019
accepted:
21
04
2020
entrez:
21
5
2020
pubmed:
21
5
2020
medline:
16
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32433536
doi: 10.1038/s42003-020-0957-6
pii: 10.1038/s42003-020-0957-6
pmc: PMC7239943
doi:
Substances chimiques
Glutarates
0
Ketoglutaric Acids
0
alpha-hydroxyglutarate
2889-31-8
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
247Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R013829/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106244/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204483/Z/16/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C8717/A18245
Pays : United Kingdom
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