Cited by 280Microbial Metabolic Engineering and BioproductionCancer, Hypoxia, and MetabolismGene Regulatory Network Analysis

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Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells

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Metallo, Christian M., Walther, Jason L., Stephanopoulos, Gregory·2009·Journal of Biotechnology

DOI 10.1016/j.jbiotec.2009.07.010PMC PMC3026314

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Abstract

(13)C metabolic flux analysis (MFA) is the most comprehensive means of characterizing cellular metabolic states. Uniquely labeled isotopic tracers enable more focused analyses to probe specific reactions within the network. As a result, the choice of tracer largely determines the precision with which one can estimate metabolic fluxes, especially in complex mammalian systems that require multiple substrates. Here we have experimentally determined metabolic fluxes in a tumor cell line, successfully recapitulating the hallmarks of cancer cell metabolism. Using these data, we computationally evaluated specifically labeled (13)C glucose and glutamine tracers for their ability to precisely and accurately estimate fluxes in central carbon metabolism. These methods enabled us to identify the optimal tracer for analyzing individual fluxes, specific pathways, and central carbon metabolism as a whole. [1,2-(13)C(2)]glucose provided the most precise estimates for glycolysis, the pentose phosphate pathway, and the overall network. Tracers such as [2-(13)C]glucose and [3-(13)C]glucose also outperformed the more commonly used [1-(13)C]glucose. [U-(13)C(5)]glutamine emerged as the preferred isotopic tracer for the analysis of the tricarboxylic acid (TCA) cycle. These results provide valuable, quantitative information on the performance of (13)C-labeled substrates and can aid in the design of more informative MFA experiments in mammalian cell culture.

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Authors: Metallo, C. M., Walther, J. L., & Stephanopoulos, G.
Affiliations: Massachusetts Institute of Technology (US)
Corresponding author: Stephanopoulos, Gregory
ORCID: Metallo, Christian M.
Walther, Jason L.
Stephanopoulos, Gregory
Venue: Journal of Biotechnology
Publisher: Elsevier BV
Published: 2009-11
Volume: 144
Issue: 3
Pages: 167-174
ISSN: 0168-1656 (ISSN-L)
DOI: 10.1016/j.jbiotec.2009.07.010
PMC: PMC3026314
OpenAlex: W2049759143
Cited by: 280
References: 35
Citations by year: 2026: 7 · 2025: 5 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 11 · 2020: 11 · 2019: 17 · 2018: 15 · 2017: 22 · 2016: 22 · 2015: 14 · 2014: 18 · 2013: 40 · 2012: 20
FWCI: 8.20
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Biotechnology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: American Cancer Society
National Institutes of Health
National Cancer Institute (R01CA160458)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075850)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords: 13C metabolic flux analysis, isotope tracers, central carbon metabolism, glycolysis, pentose phosphate pathway, TCA cycle, cancer metabolism, cancer cell lines
MeSH terms: Algorithms, Carbon, Carbon Isotopes, Computer Simulation, Glucose, Glutamine, Humans, Isotope Labeling, Confidence Intervals, Cell Line, Tumor, Metabolomics

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Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells

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