HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology
Autor: | Hermann-Georg Holzhütter, Iwona Wallach, Tilo Wünsch, Nikolaus Berndt, Martin Stockmann, David Meierhofer, Matthias König, Sascha Bulik |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Galactosemias Proteomics Carcinoma Hepatocellular Science Allosteric regulation General Physics and Astronomy Pharmacology Models Biological General Biochemistry Genetics and Molecular Biology Metabolic engineering 03 medical and health sciences Non-alcoholic Fatty Liver Disease medicine Humans Enzyme Inhibitors lcsh:Science chemistry.chemical_classification Multidisciplinary business.industry Valproic Acid Galactosemia Fatty liver Liver Neoplasms General Chemistry Metabolism medicine.disease Kinetics 030104 developmental biology Enzyme Biochemistry chemistry Liver Hepatocellular carcinoma Hepatocytes lcsh:Q business Algorithms Metabolic Networks and Pathways |
Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications |
ISSN: | 2041-1723 |
Popis: | 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). |
Databáze: | OpenAIRE |
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