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HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology

Author

Listed:
  • Nikolaus Berndt

    (Charité – Universitätsmedizin Berlin)

  • Sascha Bulik

    (Charité – Universitätsmedizin Berlin
    German Federal Institute for Risk Assessment Max-Dohrn-Straße 8-10)

  • Iwona Wallach

    (Charité – Universitätsmedizin Berlin)

  • Tilo Wünsch

    (Charité – Universitätsmedizin Berlin - Campus Virchow-Klinikum)

  • Matthias König

    (Humboldt-University Berlin)

  • Martin Stockmann

    (German Federal Institute for Risk Assessment Max-Dohrn-Straße 8-10)

  • David Meierhofer

    (Max Planck Institute of Molecular Genetics/Mass Spectroscopy)

  • Hermann-Georg Holzhütter

    (Charité – Universitätsmedizin Berlin)

Abstract

The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

Suggested Citation

  • Nikolaus Berndt & Sascha Bulik & Iwona Wallach & Tilo Wünsch & Matthias König & Martin Stockmann & David Meierhofer & Hermann-Georg Holzhütter, 2018. "HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04720-9
    DOI: 10.1038/s41467-018-04720-9
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