Evidence map›Paper›PMID 25009227›Full record

ArticleeLife2014

Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step.

Alexander A Shestov, Xiaojing Liu, Zheng Ser, Ahmad A Cluntun, Yin P Hung, Lei Huang, Dongsung Kim, Anne Le, Gary Yellen, John G Albeck and 1 more

Abstract read
In one paragraph

Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

165 citing papers in PubMed.

  1. Review
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  11. The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026
    Review
  12. Inorganic phosphate and the rapid mobilization of metabolic energy in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Review
  14. Article
  15. Frontiers in immunology · 2026
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

105 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Alexander A ShestovDivision of Nutritional Sciences, Cornell University, Ithaca, United States.
Xiaojing LiuDivision of Nutritional Sciences, Cornell University, Ithaca, United States.
Zheng SerDivision of Nutritional Sciences, Cornell University, Ithaca, United States.
Ahmad A CluntunField of Biochemistry and Molecular Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
Yin P HungDepartment of Neurobiology, Harvard Medical School, Boston, United States.
Lei HuangField of Computational Biology, Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, United States.
Dongsung KimField of Biochemistry and Molecular Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
Anne LeDepartment of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, United States.
Gary YellenDepartment of Neurobiology, Harvard Medical School, Boston, United States.
John G AlbeckDepartment of Cell Biology, Harvard Medical School, Boston, United States.
Jason W LocasaleDivision of Nutritional Sciences, Cornell University, Ithaca, United States.ORCID http://orcid.org/0000-0002-7766-3502

Funding

JHU-UMD Diabetes Research CenterP30DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BRANCATI, FREDERICK L · 2013 to 2017
$9.7M
Single cell analysis of metabolism using genetically-encoded fluorescent sensorsDP1EB016985 · NIBIB · HARVARD MEDICAL SCHOOL · PI YELLEN, GARY I · 2012 to 2016
$4.2M
The developmental layers in the CD8+ T cell response to chronic infectionR01AI110613 · NIAID · CORNELL UNIVERSITY · PI GRIMSON, ANDREW W, RUDD, BRIAN DAVID · 2014 to 2022
$4.1M
Understanding metabolic flux and the control of mammalian cell growthR00CA168997 · NCI · DUKE UNIVERSITY · PI LOCASALE, JASON W. · 2013 to 2015
$695k
NCI NIH HHS R00 CA168997NCI NIH HHS R00CA168997NIAID NIH HHS R01AI110613NIBIB NIH HHS DP1 EB016985NIDDK NIH HHS P30 DK079637
6 · The paper itself

Abstract

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.

Indexed as

Computational BiologyFructosediphosphatesGlucoseGlucose Transport Proteins, FacilitativeGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)GlycolysisHCT116 CellsHumansLactic AcidL-Lactate DehydrogenaseMass SpectrometryMetabolomicsModels, ChemicalMonte Carlo MethodPhenotypePhosphorylationfructose-1,6-diphosphateFructosediphosphatesGlucoseGlucose Transport Proteins, FacilitativeGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)Lactic AcidL-Lactate Dehydrogenasebiochemistryglucoseglycolysishumanhuman biologymass spectrometrymathematical modelingmedicinemetabolismmetabolomics

Identifiers

PMID25009227
PMCPMC4118620

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.