ArticleOpen biology2014
Inhibition of triosephosphate isomerase by phosphoenolpyruvate in the feedback-regulation of glycolysis.
Article in Open biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 109 citations in OpenAlex.
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- Glycolysis model shows that allostery maintains high ATP and limits accumulation of intermediates.Biophysical journal · 2025Article
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- Betaine supplementation affects carbohydrate metabolism in the skeletal muscle of finishing pigs.PloS one · 2025Article
- An engineered aldolase enables the biocatalytic synthesis of 2'-functionalized nucleoside analogues.Nature synthesis · 2025Article
- Article
- The metabolic function of pyruvate kinase M2 regulates reactive oxygen species production and microbial killing by neutrophils.Nature communications · 2023Article
- Increased fatty acid metabolism and decreased glycolysis are hallmarks of metabolic reprogramming within microglia in degenerating white matter during recovery from experimental stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Moonlight functions of glycolytic enzymes in cancer.Frontiers in molecular biosciences · 2023Review
- Revving an Engine of Human Metabolism: Activity Enhancement of Triosephosphate Isomerase via Hemi-Phosphorylation.ACS chemical biology · 2022Article
- Quantitative modeling of pentose phosphate pathway response to oxidative stress reveals a cooperative regulatory strategy.iScience · 2022Article
- Biogenic Volatile Organic Compounds and Protein Expressions ofPlants (Basel, Switzerland) · 2022Article
- A Multi-Omics Approach to Evaluate the Toxicity Mechanisms Associated with Silver Nanoparticles Exposure.Nanomaterials (Basel, Switzerland) · 2022Article
- Intramolecular carbon isotope signals reflect metabolite allocation in plants.Journal of experimental botany · 2022Article
- CAM Models: Lessons and Implications for CAM Evolution.Frontiers in plant science · 2022Review
- Plasma miR-193b-3p Is Elevated in Type 2 Diabetes and Could Impair Glucose Metabolism.Frontiers in endocrinology · 2022Article
- Effect of 2-Cys Peroxiredoxins Inhibition on Redox Modifications of Bull Sperm Proteins.International journal of molecular sciences · 2021Article
- pH Feedback Lifecycles Programmed by Enzymatic Logic Gates Using Common Foods as Fuels.Angewandte Chemie (International ed. in English) · 2021Article
- Counteracting the Ramifications of UVB Irradiation and Photoaging withMolecules (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The inhibition of triosephosphate isomerase (TPI) in glycolysis by the pyruvate kinase (PK) substrate phosphoenolpyruvate (PEP) results in a newly discovered feedback loop that counters oxidative stress in cancer and actively respiring cells. The mechanism underlying this inhibition is illuminated by the co-crystal structure of TPI with bound PEP at 1.6 Å resolution, and by mutational studies guided by the crystallographic results. PEP is bound to the catalytic pocket of TPI and occludes substrate, which accounts for the observation that PEP competitively inhibits the interconversion of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Replacing an isoleucine residue located in the catalytic pocket of TPI with valine or threonine altered binding of substrates and PEP, reducing TPI activity in vitro and in vivo. Confirming a TPI-mediated activation of the pentose phosphate pathway (PPP), transgenic yeast cells expressing these TPI mutations accumulate greater levels of PPP intermediates and have altered stress resistance, mimicking the activation of the PK-TPI feedback loop. These results support a model in which glycolytic regulation requires direct catalytic inhibition of TPI by the pyruvate kinase substrate PEP, mediating a protective metabolic self-reconfiguration of central metabolism under conditions of oxidative stress.
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Registered trials
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.