ArticleNature metabolism2021
Enzymatic activation of pyruvate kinase increases cytosolic oxaloacetate to inhibit the Warburg effect.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Exercise-induced protein lactylation: From molecular mechanisms to precision health applications.iScience · 2026Review
- Article
- Oxaloacetate damages mitochondria by perturbing MIC60-dependent membrane remodeling.PLoS biology · 2026Article
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Promising Role of PKM2 in the Diagnosis and Prognosis of Ovarian Cancer.Anti-cancer agents in medicinal chemistry · 2026Review
- Interaction networks of macrophage glycolysis and inflammation in sepsis: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Unveiling the inhibitory effects of tannic acid and doxorubicin combination on pyruvate kinase M2 in breast cancer cells.Frontiers in pharmacology · 2026Article
- Integrated screening for small molecules interfering with PKM2: a drug repurposing strategy against glioblastoma.Journal of translational medicine · 2025Article
- Reprogrammed glucose metabolism in vascular smooth muscle cells and its implications for vascular diseases.Pharmacological research · 2025Review
- Oxaloacetate sensing promotes innate immune antiviral defence against influenza virus infection.Nature microbiology · 2025Article
- Macrophage plasticity and glucose metabolism: the role of immunometabolism in pulmonary arterial hypertension.Clinical science (London, England : 1979) · 2025Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes.bioRxiv : the preprint server for biology · 2025Article
- The lactylation-macrophage interplay: implications for gastrointestinal disease therapeutics.Frontiers in immunology · 2025Review
- Lactate and lactylation in macrophage polarization of sepsis.Frontiers in cellular and infection microbiology · 2025Review
- Pharmacoproteomics reveals energy metabolism pathways as therapeutic targets of ivermectin in ovarian cancer toward 3P medical approaches.The EPMA journal · 2024Article
- Lactic acid induces transcriptional repression of macrophage inflammatory response via histone acetylation.Cell reports · 2024Article
- Using NMR to Monitor TET-Dependent Methylcytosine Dioxygenase Activity and Regulation.ACS chemical biology · 2024Article
- The Tricarboxylic Acid Cycle Metabolites for Cancer: Friend or Enemy.Research (Washington, D.C.) · 2024Review
- RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome.Frontiers in neurology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Pharmacological activation of the glycolytic enzyme PKM2 or expression of the constitutively active PKM1 isoform in cancer cells results in decreased lactate production, a phenomenon known as the PKM2 paradox in the Warburg effect. Here we show that oxaloacetate (OAA) is a competitive inhibitor of human lactate dehydrogenase A (LDHA) and that elevated PKM2 activity increases de novo synthesis of OAA through glutaminolysis, thereby inhibiting LDHA in cancer cells. We also show that replacement of human LDHA with rabbit LDHA, which is relatively resistant to OAA inhibition, eliminated the paradoxical correlation between the elevated PKM2 activity and the decreased lactate concentration in cancer cells treated with a PKM2 activator. Furthermore, rabbit LDHA-expressing tumours, compared to human LDHA-expressing tumours in mice, displayed resistance to the PKM2 activator. These findings describe a mechanistic explanation for the PKM2 paradox by showing that OAA accumulates and inhibits LDHA following PKM2 activation.
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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.