Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
| Autor: | Umberto Maria Battisti, Chunixa Gao, Fady Akladios, Woonghee Kim, Hong Yang, Cemil Bayram, Ismail Bolat, Metin Kiliclioglu, Nursena Yuksel, Ozlem Ozdemir Tozlu, Cheng Zhang, Jihad Sebhaoui, Shazia Iqbal, Saeed Shoaie, Ahmet Hacimuftuoglu, Serkan Yildirim, Hasan Turkez, Mathias Uhlen, Jan Boren, Adil Mardinoglu, Morten Grøtli |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Nutrients Volume 15 Issue 3 Pages: 577 |
| ISSN: | 2072-6643 |
| DOI: | 10.3390/nu15030577 |
| Popis: | Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD. |
| Databáze: | OpenAIRE |
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