Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
| dc.contributor.author | Battisti, Umberto Maria | |
| dc.contributor.author | Gao, Chunixa | |
| dc.contributor.author | Akladios, Fady | |
| dc.contributor.author | Kim, Woonghee | |
| dc.contributor.author | Yang, Hong | |
| dc.contributor.author | Bayram, Cemil | |
| dc.contributor.author | Grotli, Morten | |
| dc.date.accessioned | 2026-03-26T14:58:25Z | |
| dc.date.available | 2026-03-26T14:58:25Z | |
| dc.date.issued | 2023 | |
| dc.description | Zhang, Cheng/0000-0002-3721-8586; Kiliçlioğlu, Metin/0000-0001-9055-2164; Bayram, Cemil/0000-0001-8940-8560; Bolat, Ismail/0000-0003-1398-7046; Battisti, Umberto Maria/0000-0002-1012-8644; Mardinoglu, Adil/0000-0002-4254-6090; Iqbal, Shazia/0000-0002-5392-0930; Grøtli, Morten/0000-0003-3621-4222; Borén, Jan/0000-0003-0786-8091; Sebhaoui, Jihad/0000-0001-8197-2693; Shoaie, Saeed/0000-0001-5834-4533; Uhlen, Mathias/0000-0002-4858-8056; Özdemir, Özlem/0000-0002-5472-8174; | en_US |
| dc.description.abstract | 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. | en_US |
| dc.description.sponsorship | Knut and Alice Wallenberg Foundation; Swedish Research Council [2019-01049]; Ogonoris Foundation [0063869]; Torsten Soderberg Foundation [M105/19]; ScandiEdge Therapeutics; ScandiEdge Therapeutics; Swedish Research Council [2019-01049] Funding Source: Swedish Research Council | en_US |
| dc.description.sponsorship | The authors acknowledge financial support from the Knut and Alice Wallenberg Foundation for a proof-of-concept grant to J.B., the Swedish Research Council (Grant #: 2019-01049), the Ogonoris Foundation (Grant #: 0063869), ScandiEdge Therapeutics, and the Torsten SoederbergFoundation (Grant #: M105/19) | en_US |
| dc.identifier.doi | 10.3390/nu15030577 | |
| dc.identifier.issn | 2072-6643 | |
| dc.identifier.scopus | 2-s2.0-85147362485 | |
| dc.identifier.uri | https://doi.org/10.3390/nu15030577 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14901/3158 | |
| dc.language.iso | en | en_US |
| dc.publisher | MDPI | en_US |
| dc.relation.ispartof | Nutrients | en_US |
| dc.rights | info:eu-repo/semantics/openAccess | en_US |
| dc.subject | NAFLD | en_US |
| dc.subject | Liver Pyruvate Kinase | en_US |
| dc.subject | Ellagic Acid | en_US |
| dc.subject | Urolithins | en_US |
| dc.subject | Enzyme Inhibition | en_US |
| dc.title | Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase | en_US |
| dc.type | Article | en_US |
| dspace.entity.type | Publication | |
| gdc.author.id | Zhang, Cheng/0000-0002-3721-8586 | |
| gdc.author.id | Kiliçlioğlu, Metin/0000-0001-9055-2164 | |
| gdc.author.id | Bayram, Cemil/0000-0001-8940-8560 | |
| gdc.author.id | Bolat, Ismail/0000-0003-1398-7046 | |
| gdc.author.id | Battisti, Umberto Maria/0000-0002-1012-8644 | |
| gdc.author.id | Mardinoglu, Adil/0000-0002-4254-6090 | |
| gdc.author.scopusid | 26657153500 | |
| gdc.author.scopusid | 58098057400 | |
| gdc.author.scopusid | 51763127100 | |
| gdc.author.scopusid | 57205353546 | |
| gdc.author.scopusid | 38062511600 | |
| gdc.author.scopusid | 57222196286 | |
| gdc.author.scopusid | 24484791900 | |
| gdc.author.wosid | Zhang, Cheng/L-7906-2016 | |
| gdc.author.wosid | Kiliçlioğlu, Metin/Kwu-8857-2024 | |
| gdc.author.wosid | Bayram, Cemil/Aav-2485-2021 | |
| gdc.author.wosid | Bolat, Ismail/Aau-9698-2021 | |
| gdc.author.wosid | Mardinoglu, Adil/Aas-6360-2021 | |
| gdc.author.wosid | Grøtli, Morten/A-8735-2010 | |
| gdc.author.wosid | Yildirim, Serkan/Aah-6721-2020 | |
| gdc.description.department | Erzurum Technical University | en_US |
| gdc.description.departmenttemp | [Battisti, Umberto Maria; Gao, Chunixa; Akladios, Fady; Grotli, Morten] Univ Gothenburg, Dept Chem & Mol Biol, S-41296 Gothenburg, Sweden; [Battisti, Umberto Maria; Gao, Chunixa; Akladios, Fady; Kim, Woonghee; Yang, Hong; Zhang, Cheng; Shoaie, Saeed; Uhlen, Mathias; Mardinoglu, Adil] KTH Royal Inst Technol, Sci Life Lab, S-10450 Stockholm, Sweden; [Bayram, Cemil; Hacimuftuoglu, Ahmet] Ataturk Univ, Fac Med, Dept Med Pharmacol, TR-25240 Erzurum, Turkiye; [Bolat, Ismail; Kiliclioglu, Metin; Yildirim, Serkan] Ataturk Univ, Fac Vet, Dept Pathol, TR-25240 Erzurum, Turkiye; [Yuksel, Nursena; Tozlu, Ozlem Ozdemir] Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkiye; [Zhang, Cheng] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China; [Sebhaoui, Jihad; Iqbal, Shazia] Trustlife Labs, Drug Res & Dev Ctr, TR-34774 Istanbul, Turkiye; [Shoaie, Saeed; Mardinoglu, Adil] Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England; [Turkez, Hasan] Ataturk Univ, Fac Med, Dept Med Biol, TR-25240 Erzurum, Turkiye; [Boren, Jan] Univ Gothenburg, Dept Mol & Clin Med, S-40530 Gothenburg, Sweden; [Boren, Jan] Sahlgrens Univ Hosp, S-40530 Gothenburg, Sweden | en_US |
| gdc.description.issue | 3 | en_US |
| gdc.description.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
| gdc.description.scopusquality | Q1 | |
| gdc.description.volume | 15 | en_US |
| gdc.description.woscitationindex | Science Citation Index Expanded | |
| gdc.description.wosquality | Q1 | |
| gdc.identifier.pmid | 36771285 | |
| gdc.identifier.wos | WOS:000940885800001 |