Mechanistic Details of Early Steps in Coenzyme Q Biosynthesis Pathway in Yeast
| Autor: | Fabien Pierrel, Akio Kihara, Mélanie Leroux, Ludovic Pelosi, Laurie Anne Payet, John C. Willison |
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| Přispěvatelé: | Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), 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), 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), Faculty of Pharmaceutical Sciences, Hokkaido University [Sapporo, Japan], Fondation pour la Recherche Médicale (FRM), grant number «DPM20121125553» |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Ubiquinone Clinical Biochemistry Saccharomyces cerevisiae Aldehyde dehydrogenase Parabens Biology Biochemistry 03 medical and health sciences chemistry.chemical_compound Biosynthesis Gene Expression Regulation Fungal Drug Discovery Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Tyrosine Molecular Biology Gene Pharmacology chemistry.chemical_classification 030102 biochemistry & molecular biology Aldehyde Dehydrogenase biology.organism_classification Yeast Biosynthetic Pathways 030104 developmental biology Enzyme chemistry Coenzyme Q – cytochrome c reductase Benzaldehydes biology.protein Molecular Medicine Oxidation-Reduction Gene Deletion |
| Zdroj: | Cell Chemical Biology Cell Chemical Biology, Cell Press, 2016, 23 (10), pp.1241-1250. ⟨10.1016/j.chembiol.2016.08.008⟩ Cell Chemical Biology, 2016, 23 (10), pp.1241-1250. ⟨10.1016/j.chembiol.2016.08.008⟩ |
| ISSN: | 2451-9448 2451-9456 |
| DOI: | 10.1016/j.chembiol.2016.08.008⟩ |
| Popis: | International audience; Coenzyme Q (Q) is a redox lipid that is central for the energetic metabolism of eukaryotes. The biosynthesis of Q from the aromatic precursor 4-hydroxybenzoic acid (4-HB) is understood fairly well. However, biosynthetic details of how 4-HB is produced from tyrosine remain elusive. Here, we provide key insights into this long-standing biosynthetic problem by uncovering molecular details of the first and last reactions of the pathway in the yeast Saccharomyces cerevisiae, namely the deamination of tyrosine to 4-hydroxyphenylpyruvate by Aro8 and Aro9, and the oxidation of 4-hydroxybenzaldehyde to 4-HB by Hfd1. Inactivation of the HFD1 gene in yeast resulted in Q deficiency, which was rescued by the human enzyme ALDH3A1. This suggests that a similar pathway operates in animals, including humans, and led us to propose that patients with genetically unassigned Q deficiency should be screened for mutations in aldehyde dehydrogenase genes, especially ALDH3A1. |
| Databáze: | OpenAIRE |
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