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HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.
Nature Communications ( IF 14.7 ) Pub Date : 2018-06-19 , DOI: 10.1038/s41467-018-04720-9
Nikolaus Berndt , Sascha Bulik , Iwona Wallach , Tilo Wünsch , Matthias König , Martin Stockmann , David Meierhofer , Hermann-Georg Holzhütter

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).

中文翻译:

HEPATOKIN1是基于生物化学的肝脏代谢模型,可用于医学和药理学。

非酒精性脂肪肝疾病(NAFLD)的流行需要对控制肝脏代谢对营养挑战,药物和遗传酶变异的反应的调节回路有更深入的了解。由于人类肝脏代谢的体内研究存在严重的伦理学和技术问题,因此我们开发了基于生物化学的综合性肝脏中枢代谢动力学模型,包括通过其反应物,变构效应子和激素依赖性磷酸化来调节酶活性。该模型在医学和药理学领域的基础研究和应用的效用通过模拟在营养紊乱(酒精),药物(丙戊酸盐),和遗传性酶紊乱(半乳糖血症)。使用蛋白质组学数据来衡量最大的酶活性,该模型用于突出正常肝细胞和恶性肝细胞(腺瘤和肝细胞癌)的代谢功能差异。
更新日期:2018-06-19
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