Personalised modelling of clinical heterogeneity between medium-chain acyl-CoA dehydrogenase patients ...
figshare, 2023
academicJournal
Zugriff:
Background Monogenetic inborn errors of metabolism cause a wide phenotypic heterogeneity that may even differ between family members carrying the same genetic variant. Computational modelling of metabolic networks may identify putative sources of this inter-patient heterogeneity. Here, we mainly focus on medium-chain acyl-CoA dehydrogenase deficiency (MCADD), the most common inborn error of the mitochondrial fatty acid oxidation (mFAO). It is an enigma why some MCADD patients—if untreated—are at risk to develop severe metabolic decompensations, whereas others remain asymptomatic throughout life. We hypothesised that an ability to maintain an increased free mitochondrial CoA (CoASH) and pathway flux might distinguish asymptomatic from symptomatic patients. Results We built and experimentally validated, for the first time, a kinetic model of the human liver mFAO. Metabolites were partitioned according to their water solubility between the bulk aqueous matrix and the inner membrane. Enzymes are also ...
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Personalised modelling of clinical heterogeneity between medium-chain acyl-CoA dehydrogenase patients ...
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Autor/in / Beteiligte Person: | Odendaal, Christoff ; Jager, Emmalie A. ; Martines, Anne-Claire M. F. ; Vieira-Lara, Marcel A. ; Huijkman, Nicolette C. A. ; Kiyuna, Ligia A. ; Gerding, Albert ; Wolters, Justina C. ; Heiner-Fokkema, Rebecca ; van Eunen, Karen ; Derks, Terry G. J. ; Bakker, Barbara M. |
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Veröffentlichung: | figshare, 2023 |
Medientyp: | academicJournal |
DOI: | 10.6084/m9.figshare.c.6821269 |
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