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


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).

SEEK ID: https://seek.lisym.org/publications/132

PubMed ID: 29921957

Projects: LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi)

Publication type: Not specified

Journal: Nat Commun

Citation: Nat Commun. 2018 Jun 19;9(1):2386. doi: 10.1038/s41467-018-04720-9.

Date Published: 21st Jun 2018

Registered Mode: Not specified

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Created: 20th Dec 2018 at 10:27

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