ArticleThe Journal of biological chemistry
Determining the quantitative relationship between glycolysis and GAPDH in cancer cells exhibiting the Warburg effect.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Integrative Phosphoproteomic Profiling Reveals Stage-Specific Signalling and Metabolism in Equine Melanocytic Neoplasm.Veterinary and comparative oncology · 2026Article
- Intracellular lactic acidosis reprograms glycolysis and mitochondrial anaplerosis in cancer cells.The Journal of biological chemistry · 2026Article
- The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- Aerobic glycolysis in bladder cancer: research advances and targeted therapy potential.Frontiers in oncology · 2026Review
- Respiration defects limit serine synthesis required for lung cancer growth and survival.Nature communications · 2025Article
- Metabolic Reprogramming of Urothelial Carcinoma-A Theragnostic Target for Betulinic Acid.International journal of molecular sciences · 2025Article
- Identification of housekeeping gene for future studies exploring effects of cryopreservation on gene expression in shrimp.Scientific reports · 2025Article
- The neurotoxicity of iodoacetic acid, a byproduct of drinking water disinfection.Frontiers in toxicology · 2025Review
- Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma.Journal of translational medicine · 2024Article
- Targeting the Warburg Effect in Cancer: Where Do We Stand?International journal of molecular sciences · 2024Review
- Primary metabolomics and transcriptomic techniques were used to explore the regulatory mechanisms that may influence the flavor characteristics of freshFrontiers in plant science · 2024Article
- Pioneering molecular screening for cervical precursor lesions and cervical cancer in sera.Frontiers in oncology · 2024Article
- GAPDH facilitates homologous recombination repair by stabilizing RAD51 in an HDAC1-dependent manner.EMBO reports · 2023Article
- Differential response of luminal and basal breast cancer cells to acute and chronic hypoxia.Breast cancer research and treatment · 2023Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells.International journal of molecular sciences · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies have identified GAPDH as a promising target for treating cancer and modulating immunity because its inhibition reduces glycolysis in cells (cancer cells and immune cells) with the Warburg effect, a modified form of cellular metabolism found in cancer cells. However, the quantitative relationship between GAPDH and the aerobic glycolysis remains unknown. Here, using siRNA-mediated knockdown of GAPDH expression and iodoacetate-dependent inhibition of enzyme activity, we examined the quantitative relationship between GAPDH activity and glycolysis rate. We found that glycolytic rates were unaffected by the reduction of GAPDH activity down to 19% ± 4.8% relative to untreated controls. However, further reduction of GAPDH activity below this level caused proportional reductions in the glycolysis rate. GAPDH knockdown or inhibition also simultaneously increased the concentration of glyceraldehyde 3-phosphate (GA3P, the substrate of GAPDH). This increased GA3P concentration countered the effect of GAPDH knockdown or inhibition and stabilized the glycolysis rate by promoting GAPDH activity. Mechanistically, the intracellular GA3P concentration is controlled by the Gibbs free energy of the reactions upstream of GAPDH. The thermodynamic state of the reactions along the glycolysis pathway was only affected when GAPDH activity was reduced below 19% ± 4.8%. Doing so moved the reactions catalyzed by GAPDH + PGK1 (phosphoglycerate kinase 1, the enzyme immediate downstream of GAPDH) away from the near-equilibrium state, revealing an important biochemical basis to interpret the rate control of glycolysis by GAPDH. Collectively, we resolved the numerical relationship between GAPDH and glycolysis in cancer cells with the Warburg effect and interpreted the underlying mechanism.
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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.