
Sequestration of CoA and adaptation of CoA metabolism in MCAD-knockout cell and mouse models in response to energetic stress

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Following on in silico and in vitro work, the effect of MCAD deficiency on CoA metabolism was investigated. Using a recently published HILIC-MS/MS method, free and acylated CoA species could be measured simultaneously in HepG2 MCAD-KO cells. The levels of CoA biosynthesis intermediates and total CoA was also characterised by HPLC in liver samples from MCAD-KO mice exposed to energetic stress (fasting adn cold). qPCR was applied to investigate changes in the CoA metabolism that might constitute reactions to an excessive degree of CoA sequestration. In silico modelling was used to hypothesise on the potential benefits of multifactorial, simultaneous adaptations as opposed to single-node adaptations.
SEEK ID: https://fairdomhub.org/studies/1363
Mitochondrial fatty acid oxidation in human liver
Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation
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Created: 9th May 2025 at 14:23
Last updated: 16th May 2025 at 11:43
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Projects: SilicoTryp, Multiscale modelling of state transitions in the host-microbiome-brain network, MESI-STRAT, PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Institutions: University of Groningen

I am a Professor in Medical Systems Biology and the University Medical Centre Groningen. The research in my lab is focused on complex regulation of mammalian lipid and carbohydrate metabolism, eventually aiming at network-based therapies. We combine dynamic computer simulations with quantitative metabolomics, 13C fluxomics, proteomics and transcriptome analysis, and in depth biochemical analysis. This allows to predict and understand ‘emergent’ properties, those properties that are counterintuitive ...
Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Institutions: University of Leiden
Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Institutions: University of Leiden
Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation
Institutions: University of Leiden
PoLiMeR is funded through the EU Marie Skłodowska-Curie Innovative Training Network (ITN), which drives scientific excellence and innovation. ITNs bring together universities, research institutes, industry and clinical partners from across the world to train researchers to doctorate level.
Metabolic diseases are a burden on the European population and health care system. It is increasingly recognised that individual differences with respect to history, lifestyle, and genetic make-up affect disease ...
Programme: This Project is not associated with a Programme
Public web page: http://polimer-itn.eu/
Organisms: Homo sapiens, Mus musculus, Rattus norvegicus
Submitter: Christoff Odendaal
Studies: Model analysis, Model construction, Model validation, Sequestration of CoA and adaptation of CoA metabolism in MCAD-knockout c...
Assays: ACAD activity partitioning, Comparing acyl-CoA dehydrogenase deficiencies, Computational model (in silico), HepG2 cells (in vitro), HepG2 oxygen consumption, Kinetics Minireviews, MCADD patient personalised modelling, MCADD rescue titration, Metabolic control analysis, Mice (in vivo), Models, Predicting urinary acylcarnitines under metabolic decompensation., Whole-body ketogenic flux
Snapshots: Snapshot 1
Submitter: Christoff Odendaal
Biological problem addressed: Model Analysis Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Organisms: No organisms
Models: Model notebooks, odendaal4
SOPs: No SOPs
Data files: No Data files
Snapshots: No snapshots
The behaviour of a published MCAD-KO HepG2 cell line was compared to that of a wild-type HepG2 cell line in terms of the changes in acyl-CoA and acylcarnitine levels (measured by HILIC-MS/MS) and gene expression pertaining to CoA metabolism (characterised by qPCR). Additionally, the incorporation of label from stable isotope-labelled pantothenate (vitamine B5) was over 24 hours of exposure to an energetic stressor was also investigated.
Submitter: Christoff Odendaal
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Organisms: Homo sapiens (batch)
SOPs: No SOPs
Data files: HepG2 CoA labelling data, palmitate/no-glucose ..., HepG2 acyl-CoA measurements, palmitate/low-gluc..., HepG2 acyl-CoA measurements, palmitate/no-gluco..., HepG2 acyl-CoA/acylcarnitine measurements stati..., HepG2 acyl-CoA/acylcarnitine measurements stati..., HepG2 acylcarnitine measurements, palmitate/low..., HepG2 acylcarnitine measurements, palmitate/no-..., HepG2 qPCR statistical significance, palmitate/..., HepG2 qPCR statistical significance, palmitate/..., HepG2 qPCR, palmitate/low-glucose (Fig. S11), HepG2 qPCR, palmitate/no-glucose (Fig. S9)
Snapshots: No snapshots
MCAD-KO mice (C57BL/6J background) were exposed to three different conditions: "fed", "fasting", and "fasting + cold". In this study we determined the concentration of various CoA biosynthetic intermediates (including CoA) and the expression of CoA metabolic genes in liver tissue samples from these groups of mice.
Submitter: Christoff Odendaal
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Mitochondrial fatty acid oxidation in human liver
Organisms: No organisms
SOPs: No SOPs
Data files: Mice CoA biosynthetic intermediates (Fig. 4C), Mice qPCR (Fig. 4E-F)
Snapshots: No snapshots
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: Mice (in vivo)
The expression of various genes related to the CoA metabolism as measured by qPCR.
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: Mice (in vivo)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Incorporation of stable isotope from pantothenate into total and free CoA pools.
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Creator: Christoff Odendaal
Submitter: Christoff Odendaal
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: HepG2 cells (in vitro)
Unzip model notebooks and keep in the same folder. Notebook "0, generate_model.nb" needs to be run before the others can be, as the model needs to be exported as Excel files before they cvan be used to make the figures.
Creators: Christoff Odendaal, Barbara Bakker
Submitter: Christoff Odendaal
Model type: Ordinary differential equations (ODE)
Model format: Mathematica
Environment: JWS Online
Organism: Homo sapiens
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: Computational model (in silico)
Creators: Christoff Odendaal, Ligia Akemi Kiyuna, Madhulika Singh, Barbara Bakker, Amy HARMS, Thomas Hankemeier
Submitter: Christoff Odendaal
Model type: Not specified
Model format: Not specified
Environment: Not specified
Organism: Not specified
Investigations: Mitochondrial fatty acid oxidation in human liver
Studies: Sequestration of CoA and adaptation of CoA meta...
Assays: Computational model (in silico)