Respective roles of the microsomal ethanol oxidizing system and catalase in ethanol metabolism by deermice lacking alcohol dehydrogenase |
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| Authors: | S Kato J Alderman C S Lieber |
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| Affiliation: | 1. AP-HP, Hôpital Jean Verdier, Liver Unit, Bondy, France;2. University Paris 13, Sorbonne Paris Cité, “équipe labellisée Ligue Contre le Cancer” F-93000 Bobigny, France;3. Inserm, UMR-1162 « Functional Genomics of Solid Tumors », F-75010 Paris, France;4. SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France;5. Liver Unit, CHU, Nantes, France;6. Liver Unit, University Hospital, Tours, France;7. Liver Unit, University Hospital, Angers, France;8. Liver Unit, APHP, Avicenne, Bobigny, France;9. Liver Unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Belgium;10. Liver Unit, University Hospital, Lille, France;11. Liver Unit, University Hospital, Caen, France;12. Univ Rennes, INSERM, INRA, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), F-35000 Rennes, France;13. Liver Unit, University Hospital, Rouen, France;14. Liver Unit, University Hospital, Amiens, France;15. Liver Unit, APHP, CHU Saint-Antoine, Paris, France;16. Liver Unit, APHP, CHU Paul Brousse, Villejuif, France;17. Université Paris Descartes, APHP, Liver Unit, Hôpital Cochin, INSERM U1223, Institut Pasteur, Paris, France;18. Hepatology Unit, University Hospital, CHU Bordeaux, France;19. Liver Unit, APHP, CHU Lariboisière, Paris, France;20. Liver Unit, University Hospital, Haine Saint-Paul, Belgium;21. Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, France;22. Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, “Hepatic Complications in Obesity”, Nice F-06204, Cedex 3, France;23. University Hospital of Nice, Digestive Centre, Nice F-06202, Cedex 3, France;24. Liver Unit, University Hospital, Béclère, APHP, Clamart, France;25. Liver Unit, APHP, CHU Tenon, Paris, France;26. Clinique d’hépato-gastroentérologie pôle Digidune CHU de Grenoble, France;1. H. Buniatian Institute of Biochemistry, NAS, 5/1 Paruyr Sevak Street, Yerevan 0014, Armenia;2. Yerevan State University, Alek Manukyan 1, Yerevan, Armenia;1. College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, PR China;2. Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, PR China |
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| Abstract: | To evaluate the roles of MEOS (microsomal ethanol oxidizing system) and catalase in non-alcohol dehydrogenase (ADH) ethanol metabolism, MEOS and catalase activities in vitro and ethanol oxidation rates in hepatocytes from ADH-negative deermice were measured after treatment with catalase inhibitors and/or a stimulator of H2O2 generation. Inhibition of ethanol peroxidation by 3-amino-1,2,4-triazole (aminotriazole) was found to be greater than 85% up to 3 h and 80% at 6 h in liver homogenates. Urate (1 mM) which stimulates H2O2 production in living systems, increased ethanol oxidation fourfold in control but not in cells from aminotriazole-treated animals, documenting effective inhibition of catalase-mediated ethanol peroxidation by aminotriazole. While aminotriazole slightly depressed (15%) basal ethanol oxidation in hepatocytes, in vitro experiments showed a similar decrease in MEOS activity after aminotriazole pretreatment. Azide (0.1 mM), a potent inhibitor of catalase in vitro, also did not affect ethanol oxidation in control cells. By contrast, 1-butanol, a competitive inhibitor of MEOS, but neither a substrate nor an inhibitor of catalase, decreased ethanol oxidation rates in a dose-dependent manner. These results show that, in deermice lacking ADH, catalase plays little if any role in hepatic ethanol oxidation, and that MEOS mediates non-ADH metabolism. |
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