Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase

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Battisti U. M., Gao C., Akladios F., Kim W., Yang H., BAYRAM C., ...Daha Fazla

NUTRIENTS, cilt.15, sa.3, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 3
  • Basım Tarihi: 2023
  • Doi Numarası: 10.3390/nu15030577
  • Dergi Adı: NUTRIENTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, CINAHL, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: NAFLD, liver pyruvate kinase, ellagic acid, urolithins, enzyme inhibition, DISEASE, FLAVONOIDS, CONVERSION, ISOENZYMES, NUTRIENT, CK2
  • Atatürk Üniversitesi Adresli: Evet

Özet

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.