ArticleMolecular bioSystems2016
Simultaneous tracing of carbon and nitrogen isotopes in human cells.
Article in Molecular bioSystems, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Deciphering the Metabolic Basis and Molecular Circuitry of the Warburg Paradox in Lymphoma.Cancers · 2024Article
- One-shotMolecular systems biology · 2023Article
- Validation-based model selection for 13C metabolic flux analysis with uncertain measurement errors.PLoS computational biology · 2022Article
- Chemical Isotope Labeling LC-MS for Metabolomics.Advances in experimental medicine and biology · 2021Article
- Cellular sensing of extracellular purine nucleosides triggers an innate IFN-β response.Science advances · 2020Article
- Analysing central metabolism in ultra-high resolution: At the crossroads of carbon and nitrogen.Molecular metabolism · 2020Review
- Article
- The Design of FluxML: A Universal Modeling Language forFrontiers in microbiology · 2019Article
- Profiling the Metabolism of Human Cells by DeepCell chemical biology · 2018Article
- High-Speed Tracer Analysis of Metabolism (HS-TrAM).Wellcome open research · 2018Article
- Estimation of flux ratios without uptake or release data: Application to serine and methionine metabolism.Metabolic engineering · 2017Article
- Modeling framework for isotopic labeling of heteronuclear moieties.Journal of cheminformatics · 2017Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Stable isotope tracing is a powerful method for interrogating metabolic enzyme activities across the metabolic network of living cells. However, most studies of mammalian cells have used (13)C-labeled tracers only and focused on reactions in central carbon metabolism. Cellular metabolism, however, involves other biologically important elements, including nitrogen, hydrogen, oxygen, phosphate and sulfur. Tracing stable isotopes of such elements may help shed light on poorly understood metabolic pathways. Here, we demonstrate the use of high-resolution mass spectrometry to simultaneously trace carbon and nitrogen metabolism in human cells cultured with (13)C- and (15)N-labeled glucose and glutamine. To facilitate interpretation of the complex isotopomer data generated, we extend current methods for metabolic flux analysis to handle multivariate mass isotopomer distributions (MMIDs). We find that observed MMIDs are broadly consistent with known biochemical pathways. Whereas measured (13)C MIDs were informative for central carbon metabolism, (15)N isotopes provided evidence for nitrogen-carrying reactions in amino acid and nucleotide metabolism. This computational and experimental methodology expands the scope of metabolic flux analysis beyond carbon metabolism, and may prove important to understanding metabolic phenotypes in health and disease.
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Registered trials
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