The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step
Open accessAbstract
Aerobic glycolysis or the Warburg Effect (WE) is characterized by the increased metabolism of glucose to lactate. It remains unknown what quantitative changes to the activity of metabolism are necessary and sufficient for this phenotype. We developed a computational model of glycolysis and an integrated analysis using metabolic control analysis (MCA), metabolomics data, and statistical simulations. We identified and confirmed a novel mode of regulation specific to aerobic glycolysis where flux through GAPDH, the enzyme separating lower and upper glycolysis, is the rate-limiting step in the pathway and the levels of fructose (1,6) bisphosphate (FBP), are predictive of the rate and control points in glycolysis. Strikingly, negative flux control was found and confirmed for several steps thought to be rate-limiting in glycolysis. Together, these findings enumerate the biochemical determinants of the WE and suggest strategies for identifying the contexts in which agents that target glycolysis might be most effective.
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Cites
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
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Metabolic control analysis: a survey of its theoretical and experimental development
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The diverse functions of GAPDH: Views from different subcellular compartments
Tristan, C., Shahani, N., Sedlak, T. W., & Sawa, A. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2010.08.003 · Cited by 663
Shifts in growth strategies reflect tradeoffs in cellular economics
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PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells
Israelsen, W. J., Dayton, T. L., Davidson, S. M., Fiske, B. P., Hosios, A. M., Bellinger, G., Li, J., Yu, Y., Sasaki, M., Horner, J. W., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.025 · Cited by 549 · cited 2×
“Although the finding that pyruvate kinase typically does not exert substantial control over glycolysis may appear surprising, this finding is consistent with studies that have observed only modest changes in glycolytic flux due to changes in pyruvate kinase activity (Christofk et al., 2008; Israelsen et al., 2013).”
ResultImaging cytosolic NADH-NAD(+) redox state with a genetically encoded fluorescent biosensor
Hung, Y. P., Albeck, J. G., Tantama, M., & Yellen, G. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.012 · Cited by 509
Metabolic flux and the regulation of mammalian cell growth
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Self-citationShlomi, T., Benyamini, T., Gottlieb, E., Sharan, R., & Ruppin, E. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002018 · Cited by 244
Cited by
The Warburg Effect: How Does it Benefit Cancer Cells?
Liberti, M. V., & Locasale, J. W. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.12.001 · Cited by 5,150
Self-citationVaupel, P., Schmidberger, H., & Mayer, A. (2019) · International Journal of Radiation Biology · doi:10.1080/09553002.2019.1589653 · Cited by 893
Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity
Kornberg, M. D., Bhargava, P., Kim, P. M., Putluri, V., Snowman, A. M., Putluri, N., Calabresi, P. A., & Snyder, S. H. (2018) · Science · doi:10.1126/science.aan4665 · Cited by 687
Hosios, A. M., Hecht, V. C., Danai, L. V., Johnson, M. O., Rathmell, J. C., Steinhauser, M. L., Manalis, S. R., & Vander Heiden, M. G. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.02.012 · Cited by 641
Balmer, M. L., Ma, E. H., Bantug, G. R., Grählert, J., Pfister, S., Glatter, T., Jauch, A., Dimeloe, S., Slack, E., Dehio, P., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.03.016 · Cited by 361
Metadata
- Authors
- Shestov, A. A., Liu, X., Ser, Z., Cluntun, A. A., Hung, Y. P., Huang, L., Kim, D., Le, A., Yellen, G., Albeck, J. G., & Locasale, J. W.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2014-07-09
- Volume
- 3
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2153041190
- Cited by
- 315
- References
- 14
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- gold
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- Shestov, A. A., Liu, X., Ser, Z., Cluntun, A. A., Hung, Y. P., Huang, L., Kim, D., Le, A., Yellen, G., Albeck, J. G., & Locasale, J. W. (2014). Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step. eLife. https://doi.org/10.7554/elife.03342
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