Coenzyme Q Biosynthesis: Coq6 Is Required for the C5-Hydroxylation Reaction and Substrate Analogs Rescue Coq6 Deficiency
| Autor: | Marc Fontecave, Mohammad Ozeir, Roland Lill, Ulrich Mühlenhoff, Fabien Pierrel, Holger Webert |
|---|---|
| Přispěvatelé: | Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut für Zytobiologie und Zytopathologie, Philipps Universität Marburg, Chaire Chimie des processus biologiques, Laboratoire de Chimie des Processus Biologiques (LCPB), Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Philipps Universität Marburg = Philipps University of Marburg, Collège de France - Chaire Chimie des processus biologiques |
| Jazyk: | angličtina |
| Předmět: |
Saccharomyces cerevisiae Proteins
Stereochemistry Ubiquinone Mutant Clinical Biochemistry Parabens Saccharomyces cerevisiae Biology Hydroxylation Biochemistry Article 03 medical and health sciences chemistry.chemical_compound Biosynthesis COQ6 Drug Discovery Hydroxybenzoates [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology Ferredoxin Chromatography High Pressure Liquid 030304 developmental biology chemistry.chemical_classification Pharmacology Vanillic Acid 0303 health sciences 030302 biochemistry & molecular biology Adrenodoxin Membrane Proteins General Medicine Monooxygenase Ferredoxin-NADP Reductase Enzyme chemistry Coenzyme Q – cytochrome c reductase Mutation Molecular Medicine |
| Zdroj: | Chem Biol Chem Biol, 2011, 18 (9), pp.1134-42. ⟨10.1016/j.chembiol.2011.07.008⟩ |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/j.chembiol.2011.07.008 |
| Popis: | International audience; Coenzyme Q (Q), an essential component of eukaryotic cells, is synthesized by several enzymes from the precursor 4-hydroxybenzoic acid. Mutations in six of the Q biosynthesis genes cause diseases that can sometimes be ameliorated by oral Q supplementation. We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. In an unusual way, the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in vivo source of electrons for Coq6. We also show that hydroxylated analogs of 4-hydroxybenzoic acid, such as vanillic acid or 3,4-dihydroxybenzoic acid, restore Q biosynthesis and respiration in a Saccharomyces cerevisiae coq6 mutant. Our results demonstrate that appropriate analogs of 4-hydroxybenzoic acid can bypass a deficient Q biosynthetic enzyme and might be considered for the treatment of some primary Q deficiencies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|