Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene susceptibility variants
| العنوان: | Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene susceptibility variants |
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| المؤلفون: | Magalie Barth, Claire Sechter, Anne-Frédérique Dessein, Marie-Christine Minot-Myhié, Gilbert Briand, Claire Douillard, Arnaud Lacour, Delphine Lamireau, Christine Vianey-Saban, Marie Joncquel-Chevalier Curt, Monique Fontaine, Karine Mention-Mulliez, Joseph Vamecq, Niels Gregersen, Isabelle Redonnet-Vernhet, Pascale de Lonlay, Alice Kuster, Cécile Acquaviva, Dries Dobbelaere |
| المساهمون: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | Dessein, A-F, Fontaine, M, Joncquel-Chevalier Curt, M, Briand, G, Sechter, C, Mention-Mulliez, K, Dobbelaere, D, Douillard, C, Lacour, A, Redonnet-Vernhet, I, Lamireau, D, Barth, M, Minot-Myhié, M-C, Kuster, A, de Lonlay, P, Gregersen, N, Acquaviva, C, Vianey-Saban, C & Vamecq, J 2017, ' Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene susceptibility variants ', Clinica chimica acta; international journal of clinical chemistry, vol. 471, pp. 101-106 . https://doi.org/10.1016/j.cca.2017.05.026Test Clinica Chimica Acta Clinica Chimica Acta, Elsevier, 2017, 471, pp.101-106. ⟨10.1016/j.cca.2017.05.026⟩ |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, ACADS pathogenic mutation, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Palmitic Acid, Dehydrogenase, SCAD functional, Compound heterozygosity, SCAD GENE, Biochemistry, Acyl-CoA Dehydrogenase, chemistry.chemical_compound, POPULATION, chemistry.chemical_classification, NEWBORN BLOOD SPOTS, ACADS Short-chain acyl-CoA dehydrogenase [SCAD], education.field_of_study, In situ fluxomic assessment, General Medicine, Mitochondria, DEFICIENCY, Phenotype, Child, Preschool, Female, Oxidation-Reduction, impairment, Genotype, Population, ACADS susceptibility variants (c.511C \textgreater T, SCAD deficiency, Biology, FREQUENCY, Polymorphism, Single Nucleotide, ACADS, 03 medical and health sciences, Biosynthesis, Journal Article, Humans, Genetic Predisposition to Disease, education, Gene, COMMON, Biochemistry (medical), Infant, Newborn, Fatty acid, Infant, Molecular biology, of protein function, Metabolic Flux Analysis, 030104 developmental biology, Enzyme, chemistry, and c.625G \textgreater A) |
| الوصف: | International audience; Background: Despite ACADS (aryl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C \textgreater T and c.625G \textgreater A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether or not, they might affect overall fatty acid beta-oxidation still remains, however, unclear. Methods: De novo biosynthesis of acylcarnitines by whole blood samples incubated with deuterated palmitate (16-H-2(3),15-H-2(2)-palmitate) is suitable as a fluxomic exploration to distinguish between normal and disrupted beta-oxidation, abnormal profiles and ratios of acylcarnitines with different chain-lengths being indicative of the site for enzymatic blockade. Determinations in 301 control subjects of ratios between deuterated butyrylcarnitine and sum of deuterated C2 to C14 acylcarnitines served here as reference values to state specifically functional SCAD impairment in patients addressed for clinical and/or biological suspicion of a beta-oxidation disorder. Results: Functional SCAD impairment was found in 39 patients. The 27 patients accepting subsequent gene studies were all positive for ACADS mutations. Twenty-six of 27 patients were positive for c.625G \textgreater A variant. Twenty-three of 27 patients harbored susceptibility variants as sole ACADS alterations (18 homozygous and 3 heterozygous for c.625G \textgreater A, 2 compound heterozygous for c.625G \textgreater A/c.511C \textgreater T). Conclusion: Our present fluxomic assessment of SCAD suggests a link between ACADS susceptibility variants and abnormal beta-oxidation consistent with known altered kinetics of these variants. |
| تدمد: | 1873-3492 0009-8981 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b7e1f694689d47fbb9ea3ffac5ba347Test https://pubmed.ncbi.nlm.nih.gov/28532786Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....8b7e1f694689d47fbb9ea3ffac5ba347 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18733492 00098981 |
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