Functional and structural impact of 10 ACADM missense mutations on human medium chain acyl-Coa dehydrogenase

Functional and structural impact of 10 ACADM missense mutations on human medium chain acyl-Coa dehydrogenase

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is associated with ACADM gene mutations, leading to an impaired function and/or structure of MCAD. Importantly, after import into the mitochondria, MCAD must incorporate a molecule of flavin adenine dinucleotide (FAD) per subunit and asse...

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Veröffentlicht in:Biochimica et biophysica acta. Molecular basis of disease 2023-10, Vol.1869 (7), p.166766-166766, Article 166766
Hauptverfasser: Madeira, Catarina A., Anselmo, Carolina, Costa, João M., Bonito, Cátia A., Ferreira, Ricardo J., Santos, Daniel J.V.A., Wanders, Ronald J., Vicente, João B., Ventura, Fátima V., Leandro, Paula
Format: Artikel
Sprache:eng
Schlagworte:
Acyl-CoA Dehydrogenase - genetics
Acyl-CoA Dehydrogenase - metabolism
Disease-causing mutations
Electron transferring flavoprotein
Flavin adenine dinucleotide
Flavin-Adenine Dinucleotide - metabolism
Humans
Inborn metabolic disorders
Medium chain acyl-CoA dehydrogenase deficiency
Mutation
Mutation, Missense
Protein misfolding
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Zusammenfassung:Medium chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is associated with ACADM gene mutations, leading to an impaired function and/or structure of MCAD. Importantly, after import into the mitochondria, MCAD must incorporate a molecule of flavin adenine dinucleotide (FAD) per subunit and assemble into tetramers. However, the effect of MCAD amino acid substitutions on FAD incorporation has not been investigated. Herein, the commonest MCAD variant (p.K304E) and 11 additional rare variants (p.Y48C, p.R55G, p.A88P, p.Y133C, p.A140T, p.D143V, p.G224R, p.L238F, p.V264I, p.Y372N, and p.G377V) were functionally and structurally characterized. Half of the studied variants presented a FAD content
ISSN:0925-4439
1879-260X
DOI:10.1016/j.bbadis.2023.166766