دورية أكاديمية
Phytol-induced pathology in 2-hydroxyacyl-CoA lyase (HACL1) deficient mice. Evidence for a second non-HACL1-related lyase.
| العنوان: | Phytol-induced pathology in 2-hydroxyacyl-CoA lyase (HACL1) deficient mice. Evidence for a second non-HACL1-related lyase. |
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| المؤلفون: | Mezzar S; LIPIT, Department of Cellular and Molecular Medicine, KU Leuven, Belgium., De Schryver E; LIPIT, Department of Cellular and Molecular Medicine, KU Leuven, Belgium., Asselberghs S; LIPIT, Department of Cellular and Molecular Medicine, KU Leuven, Belgium., Meyhi E; LIPIT, Department of Cellular and Molecular Medicine, KU Leuven, Belgium., Morvay PL; LIPIT, Department of Cellular and Molecular Medicine, KU Leuven, Belgium., Baes M; Laboratory for Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium., Van Veldhoven PP; LIPIT, Department of Cellular and Molecular Medicine, KU Leuven, Belgium. Electronic address: paul.vanveldhoven@med.kuleuven.be. |
| المصدر: | Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2017 Sep; Vol. 1862 (9), pp. 972-990. Date of Electronic Publication: 2017 Jun 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101731727 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1388-1981 (Print) Linking ISSN: 13881981 NLM ISO Abbreviation: Biochim Biophys Acta Mol Cell Biol Lipids Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier |
| مواضيع طبية MeSH: | Enoyl-CoA Hydratase/*deficiency , Enoyl-CoA Hydratase/*metabolism , Lyases/*metabolism , Phytol/*pharmacology, Animals ; Disease Models, Animal ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; Fatty Acids/pharmacology ; Female ; Liver/drug effects ; Liver/metabolism ; Male ; Mice ; Mice, Knockout ; Oxidation-Reduction ; PPAR alpha/metabolism ; Phytanic Acid/pharmacology |
| مستخلص: | 2-Hydroxyacyl-CoA lyase (HACL1) is a key enzyme of the peroxisomal α-oxidation of phytanic acid. To better understand its role in health and disease, a mouse model lacking HACL1 was investigated. Under normal conditions, these mice did not display a particular phenotype. However, upon dietary administration of phytol, phytanic acid accumulated in tissues, mainly in liver and serum of KO mice. As a consequence of phytanic acid (or a metabolite) toxicity, KO mice displayed a significant weight loss, absence of abdominal white adipose tissue, enlarged and mottled liver and reduced hepatic glycogen and triglycerides. In addition, hepatic PPARα was activated. The central nervous system of the phytol-treated mice was apparently not affected. In addition, 2OH-FA did not accumulate in the central nervous system of HACL1 deficient mice, likely due to the presence in the endoplasmic reticulum of an alternate HACL1-unrelated lyase. The latter may serve as a backup system in certain tissues and account for the formation of pristanic acid in the phytol-fed KO mice. As the degradation of pristanic acid is also impaired, both phytanoyl- and pristanoyl-CoA levels are increased in liver, and the ω-oxidized metabolites are excreted in urine. In conclusion, HACL1 deficiency is not associated with a severe phenotype, but in combination with phytanic acid intake, the normal situation in man, it might present with phytanic acid elevation and resemble a Refsum like disorder. (Copyright © 2017 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Cerebronic acid; Mouse model; Peroxisomes; Phytanic acid; Refsum; Thiamine; α-Oxidation; ω-Oxidation |
| المشرفين على المادة: | 0 (Fatty Acids) 0 (PPAR alpha) 14721-66-5 (Phytanic Acid) 150-86-7 (Phytol) 5FMQ2908AP (pristanic acid) EC 4.- (Lyases) EC 4.2.1.17 (Enoyl-CoA Hydratase) |
| تواريخ الأحداث: | Date Created: 20170621 Date Completed: 20171019 Latest Revision: 20180919 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.bbalip.2017.06.004 |
| PMID: | 28629946 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1388-1981 |
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| DOI: | 10.1016/j.bbalip.2017.06.004 |