Mitochondrial fatty acid oxidation in human liver

No description specified

DOI: 10.15490/fairdomhub.1.investigation.587.1

Zenodo URL: None

Created at: 13th Jun 2023 at 14:53

Contents

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

Parameter Search SOP

No description specified

  • Parameter search SOP.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
Fingerprints

These checksums allow you to check a Snapshot you have downloaded hasn't been modified. For details on how to use these please visit this guide

MD5: e51d5f16c7e0fc7c9dbbffcca6badb12

SHA1: 130f08185a17332c842422e0ee9905a9f9fd1b9d

Citation
Odendaal, C., Bakker, B., Jager, E., & Derks, T. G. J. (2023). Mitochondrial fatty acid oxidation in human liver. FAIRDOMHub. https://doi.org/10.15490/FAIRDOMHUB.1.INVESTIGATION.587.1
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Snapshot 1 (13th Jun 2023) DOI
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Created: 13th Jun 2023 at 14:53

Last updated: 13th Jun 2023 at 14:54

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