ArticleAmerican journal of physiology. Cell physiology2015
Caffeine inhibits glucose transport by binding at the GLUT1 nucleotide-binding site.
Article in American journal of physiology. Cell physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Direct targeting of GLUT1 in cancer: A decade of inhibitor discovery and medicinal chemistry insights.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Prevalence of Bruxism Among Young Adult Energy Drink Consumers in Jordan.Journal of clinical medicine · 2025Article
- Glut1 Deficiency Syndrome: Novel Pathomechanisms, Current Concepts, and Challenges.Journal of inherited metabolic disease · 2025Review
- Article
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
- The novel family of WarbicinFrontiers in oncology · 2024Article
- Discovery of New Glucose Uptake Inhibitors as Potential Anticancer Agents by Non-Radioactive Cell-Based Assays.Molecules (Basel, Switzerland) · 2022Article
- Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies.Cancers · 2022Review
- Glucose uptake as an alternative to oxygen uptake for assessing metabolic rate inCurrent research in physiology · 2022Article
- Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT-1: Influence onClinical and translational science · 2021Article
- Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms.Journal of microbiology and biotechnology · 2021Review
- Power of two: combination of therapeutic approaches involving glucose transporter (GLUT) inhibitors to combat cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Erythroid glucose transport in health and disease.Pflugers Archiv : European journal of physiology · 2020Review
- Insulin-dependent, glucose transporter 1 mediated glucose uptake and tube formation in the human placental first trimester trophoblast cells.Molecular and cellular biochemistry · 2019Article
- Article
- Kinetic Basis of Cis- and Trans-Allostery in GLUT1-Mediated Sugar Transport.The Journal of membrane biology · 2018Article
- Caffeine inhibition of GLUT1 is dependent on the activation state of the transporter.Biochimie · 2017Article
- WZB117 (2-Fluoro-6-(m-hydroxybenzoyloxy) Phenyl m-Hydroxybenzoate) Inhibits GLUT1-mediated Sugar Transport by Binding Reversibly at the Exofacial Sugar Binding Site.The Journal of biological chemistry · 2016Article
- SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy.Scientific reports · 2016Article
- Effect of nordihydroguaiaretic acid on cell viability and glucose transport in human leukemic cell lines.FEBS open bio · 2016Article
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4 authors at 1 institution in 1 country.
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Abstract
Glucose transporter 1 (GLUT1) is the primary glucose transport protein of the cardiovascular system and astroglia. A recent study proposes that caffeine uncompetitive inhibition of GLUT1 results from interactions at an exofacial GLUT1 site. Intracellular ATP is also an uncompetitive GLUT1 inhibitor and shares structural similarities with caffeine, suggesting that caffeine acts at the previously characterized endofacial GLUT1 nucleotide-binding site. We tested this by confirming that caffeine uncompetitively inhibits GLUT1-mediated 3-O-methylglucose uptake in human erythrocytes [Vmax and Km for transport are reduced fourfold; Ki(app) = 3.5 mM caffeine]. ATP and AMP antagonize caffeine inhibition of 3-O-methylglucose uptake in erythrocyte ghosts by increasing Ki(app) for caffeine inhibition of transport from 0.9 ± 0.3 mM in the absence of intracellular nucleotides to 2.6 ± 0.6 and 2.4 ± 0.5 mM in the presence of 5 mM intracellular ATP or AMP, respectively. Extracellular ATP has no effect on sugar uptake or its inhibition by caffeine. Caffeine and ATP displace the fluorescent ATP derivative, trinitrophenyl-ATP, from the GLUT1 nucleotide-binding site, but d-glucose and the transport inhibitor cytochalasin B do not. Caffeine, but not ATP, inhibits cytochalasin B binding to GLUT1. Like ATP, caffeine renders the GLUT1 carboxy-terminus less accessible to peptide-directed antibodies, but cytochalasin B and d-glucose do not. These results suggest that the caffeine-binding site bridges two nonoverlapping GLUT1 endofacial sites-the regulatory, nucleotide-binding site and the cytochalasin B-binding site. Caffeine binding to GLUT1 mimics the action of ATP but not cytochalasin B on sugar transport. Molecular docking studies support this hypothesis.
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