Snapshot 2
DownloadDOI: 10.15490/fairdomhub.1.investigation.587.2
Zenodo URL: None
Created at: 1st May 2026 at 15:06
Mitochondrial fatty acid oxidation in human liver
Model construction
No description specified
Models
No description specified
odendaal1
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
- odendaal1 (1).xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
odendaal2
Adjusted model to test the model's ability to oxygen consumption rate by permeabilised HepG2 cells in an Oroboros oxygraph. Data from [Fletcher et al. (2019)](https://insight.jci.org/articles/view/127737).
- odendaal2.xml
odendaal3
Adjusted model to test the model's ability to predict palmitoyl-CoA and octanoyl-CoA dehydrogenation in human liver lysate, with and without anti-MCAD and anti-VLCAD antibodies. Data from [Aoyama et al. (1995)](https://www.jci.org/articles/view/117947).
- odendaal3.xml
Kinetics Minireviews
Minireviews about each enzyme in the mitochindrial beta-oxidation model on which the final parameter choices (fixed-parameter model) and parameter sampling distributions (ensemble) were based.
Equilibrium constants
The theory, calculations, and conditions that went into estimating the Keqs.
- 0, Theory - Estimating the equilibrium constants.pdf
NADH and NAD+
NADH and NAD+ (Nicotinamide adinine dinucleotide) as constant values.
- 13.4, NAD and NADH.pdf
Compartment volumes
Volume per mg mitochondrial protein of mitochondrion and cytosol.
- 13.6, Compartment Volumes.pdf
Model validation
No description specified
HepG2 oxygen consumption
Validation of model's ability to predict oxygen consumption flux as measured usign permeabilised cells in an Oroboros Oxygraph. Generates Fig. 2A in the associated publication.
Download "Model_notebooks.rar", unzip, and run: "2, generate-model-Oroboros-validation-[needs(1)]-20221109.nb" and "4, Fig2A-Oroboros-simulation-data-[needs-(1-2-and-3)]-20221109.nb" after running "1, generate-model-20221109.nb"
HepG2 protein concentration for O2 consumption assay
Protein measurement used to normalised the oxygen consumption flux measured on an Oroboros oxygraph.
- 3, protein_WT_KO_PCoA_Malate_Carnitine_20230609.xlsx
Oxygen concentration and consumption flux in permeabilised HepG2 cells
Measured in an Oroboros oxygraph.
- 3, data_WT_KO_PCoA_Malate_Carnitine_20230307.xlsx
odendaal2
Adjusted model to test the model's ability to oxygen consumption rate by permeabilised HepG2 cells in an Oroboros oxygraph. Data from [Fletcher et al. (2019)](https://insight.jci.org/articles/view/127737).
- odendaal2.xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
Report: Selection of HepG2 for MCAD-KO
A short description of the experiments conducted to decide on HepG2 cells as the appropriate line for the generation of an MCAD knockout. IHH, Hep3B, HepG2, and HUH-7 cells were all consdered.
- Selection of HepG2 for MCAD knockout.pdf
Whole-body ketogenic flux
Validation of model's ability to predict whole-body ketogeneic flux as extracted form [Fletcher et al. (2019)](https://insight.jci.org/articles/view/127737). Generates Fig. 2B in the associated publication.
Download "Model_notebooks.rar", unzip, and run: "2, generate-model-Oroboros-validation-[needs(1)]-20221109.nb" and "5, Fig2B-ketogenesis-validation-[needs-(1)]-20221109.nb" after running "1, generate-model-20221109.nb"
odendaal1
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
- odendaal1 (1).xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
ACAD activity partitioning
Testing the model's ability to predict palmitoyl-CoA and octanoyl-CoA dehydrogenation in human liver lysate, with and without anti-MCAD and anti-VLCAD antibodies. Generates Fig. 2 C and D in the associated publication. Data from [Aoyama et al. (1995)](https://www.jci.org/articles/view/117947).
Downoad and unzip "Model_notebooks.rar" and run "6, Fig2C+D-ACAD-partitioning-validation-[needs-(1)]-20221109.nb" after running "1, generate-model-20221109.nb".
odendaal3
Adjusted model to test the model's ability to predict palmitoyl-CoA and octanoyl-CoA dehydrogenation in human liver lysate, with and without anti-MCAD and anti-VLCAD antibodies. Data from [Aoyama et al. (1995)](https://www.jci.org/articles/view/117947).
- odendaal3.xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
Model analysis
No description specified
Predicting urinary acylcarnitines under metabolic decompensation.
Prediction of patient urinary acylcarnitine under metabolic decompensation. Generates Fig. 3, Table 1, and Table S2 in the associated publication.
Download and unzip "Model_notebooks.rar" and run "7, Fig3+4+S1+S3-ACADDs-[needs-(1)]-20221109.nb" after running "1, generate-model-20221109.nb"
odendaal1
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
- odendaal1 (1).xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
Metabolic control analysis
Calculation of control and response coefficients. Generates Fig. 5, Fig. S4, and Table S2 in the associated publication.
Download "Model_notebooks.rar", unzip, and run: "8, Fig5-control-coefficients-[needs-(1)]-20221109.nb", "9, TableS2-response-coefficients-[needs-(1)]-20230302.nb", and "15, FigS4-control-coefficients-low-AcetylCoA-[needs-(1)]-20221109.nb" after running "1, generate-model-20221109.nb"
odendaal1
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
- odendaal1 (1).xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
Comparing acyl-CoA dehydrogenase deficiencies
Based on odendaal1, a control model is made and compared to model deficient for short-chain acyl-CoA dehydrogenase (SCADD, 0%), medium-chain acyl-CoA dehydrogenase (MCADD, 0%), and very long-chain acyl-CoA dehydrogenase (VLCADD, 10%). With and withou metabolite partitioning, and with a fixed mitohondrial free CoASH. Generates Figures 3, 4, S1, S2, and S3 in the related paper.
Download "Model_notebooks.rar", unzip, and run: "7, Fig3+4+S1+S3-ACADDs-[needs-(1)]-20221109.nb" and "14,
...
odendaal1
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
- odendaal1 (1).xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
MCADD rescue titration
Incrementally increase the activity of some target rescue enzymes from 20% of default expression to 200% of default expression in a control and MCADD model to see if flux and CoASH concentration are rescued. Generates Fig. 6, S5, and S6.
Download "Model_notebooks.rar", unzip, and run "11, Fig6+S5-rescues-[needs-(1-and-10)]-20221109.nb", "10, Fig6B-inset-rescues-(low-acetylCoA)-[needs-(1)]-20221109.nb", and "16, FigS6-rescues-20221109-fixed-[needs-(1)]-CoASH.nb" after running "1, generate-model-20221109.nb"
...
odendaal1
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
- odendaal1 (1).xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
MCADD patient personalised modelling
Creation of personalised models of control, symptomatic MCADD, asymptomatic MCADD, and early diagnosis MCADD individuals using fibroblast proteomics to adjust model Vmaxes. Generates Fig. 7 and S7.
Download and unzip "Model_notebooks.rar" and run "13, Fig7-personalised-models-[needs-(1-and-12)]-20221109.nb" after running "1, generate-model-20221109.nb" and "12, Fig7-S7-preprocessing-[needs-(1)-]-20221109.nb".
Fibroblasts proteomics
Proteomics from MCADD and control individuals' fibroblasts.
- Fibroblast proteomics.xlsx
odendaal1
Human mitochondrial fatty acid oxidation of saturated, even chain acyl-Coas beginning at C16. See Model description for detail.
- odendaal1 (1).xml
Model notebooks
Unzip model notebooks and keep in the same folder. Notebook names state which notebooks need to be run before them in order for them to word, e.g. "[needs-(1)]" indicates that the notebook numbered 1 must be run and its exported output generated before the given notebook can work. This has to do with the model being generated in only one notebook to avoid duplication.
- Model_notebooks.zip
Sequestration of CoA and adaptation of CoA metabolism in MCAD-knockout cell and mouse models in response to energetic stress
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
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Computational model (in silico)
No description specified
Model notebooks
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.
- model_notebooks.zip
HepG2 cells (in vitro)
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.
HepG2 acylcarnitine measurements, palmitate/no-glucose (Fig. 2, Fig. S2, Fig. S7)
No description specified
- data_Fig2_FigS2_FigS7_acylcarnitine_hepG2_palm_no_gluc.xlsx
HepG2 acyl-CoA measurements, palmitate/no-glucose (Fig. 2, Fig. S3, Fig. S7)
No description specified
- data_Fig2_FigS3_FigS7_acyl_CoA_hepG2_palm_no_gluc.xlsx
HepG2 CoA labelling data, palmitate/no-glucose (Fig. 3, Fig. S8, Tables S1-S4)
Incorporation of stable isotope from pantothenate into total and free CoA pools.
- data_Fig3_FigS8_TablesS1-S4_labelling_experiment_hepG2_palm_no_gluc.xlsx
HepG2 acyl-CoA measurements, palmitate/low-glucose (Fig.S5, Fig. S7)
No description specified
- data_FigS5_FigS7_acyl_CoA_hepG2_palm_low_gluc.xlsx
HepG2 acylcarnitine measurements, palmitate/low-glucose (Fig. S5, Fig. S7)
No description specified
- data_FigS5_FigS7_acylcarnitine_hepG2_palm_low_gluc.xlsx
HepG2 acyl-CoA/acylcarnitine measurements statistical significance, palmitate/low-glucose (Fig. S6)
No description specified
- data_FigS6_acyl_CoA_acylcarnitine_significance_hepG2_palm_low_gluc.xlsx
HepG2 acyl-CoA/acylcarnitine measurements statistical significance, palmitate/no-glucose (Fig. S4)
No description specified
- data_FigS4_acyl_CoA_acylcarnitine_significance_hepG2_palm_no_gluc.xlsx
HepG2 qPCR, PANK isoform expression (Fig. S9)
No description specified
- data_FigS9_hepG2_qPCR_panks.xlsx
HepG2 qPCR, palmitate/no-glucose (Fig. S11)
No description specified
- data_FigS11_hepG2_qPCR_palm_no_gluc.xlsx
HepG2 qPCR statistical significance, palmitate/no-glucose (Fig. S12)
No description specified
- data_FigS12_hepG2_qPCR_significance_palm_no_gluc.xlsx
HepG2 qPCR, palmitate/low-glucose (Fig. S13)
No description specified
- data_FigS13_hepG2_qPCR_palm_low_gluc.xlsx
HepG2 qPCR statistical significance, palmitate/low-glucose (Fig. S14)
No description specified
- data_FigS14_hepG2_qPCR_significance_palm_low_gluc.xlsx
Mice (in vivo)
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.
Mice CoA biosynthetic intermediates (Fig. 4C)
No description specified
- data_Fig4C_mice_CoA_biosynthesis_intermediates.xlsx
Mice qPCR (Fig. 4E-F)
The expression of various genes related to the CoA metabolism as measured by qPCR.
- data_Fig4D-E_mice_qPCR.xlsx
Mouse liver body temperature (Fig. S10)
No description specified
- data_FigS10_mice_body_temperature.xlsx
Ensemble modelling of human mitochondrial fatty acid oxidation
Considering parameter uncertainty explicitly by generating 50 models.
Ensemble kinetic model
Explicit consideration of kinetic paramater uncertainty as obtained from literature.
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Created: 1st May 2026 at 15:06
Last updated: 1st May 2026 at 15:07
