ArticleThe Journal of biological chemistry2011
Green tea polyphenols control dysregulated glutamate dehydrogenase in transgenic mice by hijacking the ADP activation site.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 76 citations in OpenAlex.
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- Effectiveness of Tri-Kaysorn-Mas Extract in Ameliorating Cognitive-like Behavior Deficits in Ovariectomized Mice via Activation of Multiple Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Evolutionary Changes in Primate Glutamate Dehydrogenases 1 and 2 Influence the Protein Regulation by Ligands, Targeting and Posttranslational Modifications.International journal of molecular sciences · 2024Review
- Suppressive effect of Yokukansan on glutamate released from canine keratinocytes.Open veterinary journal · 2024Article
- Glutaminolysis is a Potential Therapeutic Target for Kidney Diseases.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer.Frontiers in oncology · 2023Review
- The Mitochondrial Protein MitoNEET as a Probe for the Allostery of Glutamate Dehydrogenase.Molecules (Basel, Switzerland) · 2022Article
- Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022Review
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- Chemical signaling in the developing avian retina: Focus on cyclic AMP and AKT-dependent pathways.Frontiers in cell and developmental biology · 2022Review
- PGK1 : An Essential Player in Modulating Tumor Metabolism.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Mechanistic Insights into Biological Activities of Polyphenolic Compounds from Rosemary Obtained by Inverse Molecular Docking.Foods (Basel, Switzerland) · 2021Article
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- Mapping the Intramolecular Communications among Different Glutamate Dehydrogenase States Using Molecular Dynamics.Biomolecules · 2021Article
- Glutamine Metabolism in Cancer.Advances in experimental medicine and biology · 2021Article
- Natural Products and Derivatives Targeting at Cancer Energy Metabolism: A Potential Treatment Strategy.Current medical science · 2020Review
- Canagliflozin impairs blood reperfusion of ischaemic lower limb partially by inhibiting the retention and paracrine function of bone marrow derived mesenchymal stem cells.EBioMedicine · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and, in animals, is extensively regulated by a number of metabolites. Gain of function mutations in GDH that abrogate GTP inhibition cause the hyperinsulinism/hyperammonemia syndrome (HHS), resulting in increased pancreatic β-cell responsiveness to leucine and susceptibility to hypoglycemia following high protein meals. We have previously shown that two of the polyphenols from green tea (epigallocatechin gallate (EGCG) and epicatechin gallate (ECG)) inhibit GDH in vitro and that EGCG blocks GDH-mediated insulin secretion in wild type rat islets. Using structural and site-directed mutagenesis studies, we demonstrate that ECG binds to the same site as the allosteric regulator, ADP. Perifusion assays using pancreatic islets from transgenic mice expressing a human HHS form of GDH demonstrate that the hyperresponse to glutamine caused by dysregulated GDH is blocked by the addition of EGCG. As observed in HHS patients, these transgenic mice are hypersensitive to amino acid feeding, and this is abrogated by oral administration of EGCG prior to challenge. Finally, the low basal blood glucose level in the HHS mouse model is improved upon chronic administration of EGCG. These results suggest that this common natural product or some derivative thereof may prove useful in controlling this genetic disorder. Of broader clinical implication is that other groups have shown that restriction of glutamine catabolism via these GDH inhibitors can be useful in treating various tumors. This HHS transgenic mouse model offers a highly useful means to test these agents in vivo.
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