title: HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology.
abstract: We present HepatoNet1, the first reconstruction of a comprehensive metabolic network of the human hepatocyte that is shown to accomplish a large canon of known metabolic liver functions. The network comprises 777 metabolites in six intracellular and two extracellular compartments and 2539 reactions, including 1466 transport reactions. It is based on the manual evaluation of >1500 original scientific research publications to warrant a high-quality evidence-based model. The final network is the result of an iterative process of data compilation and rigorous computational testing of network functionality by means of constraint-based modeling techniques. Taking the hepatic detoxification of ammonia as an example, we show how the availability of nutrients and oxygen may modulate the interplay of various metabolic pathways to allow an efficient response of the liver to perturbations of the homeostasis of blood compounds.
authors.affiliation: Institute of Biochemistry, University Medicine Charité Berlin, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gille
authors.forename: Christian
authors.initials: C
authors.lastname: Bölling
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoppe
authors.forename: Sascha
authors.initials: S
authors.lastname: Bulik
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Katrin
authors.initials: K
authors.lastname: Hübner
authors.forename: Anja
authors.initials: A
authors.lastname: Karlstädt
authors.forename: Ramanan
authors.initials: R
authors.lastname: Ganeshan
authors.forename: Matthias
authors.initials: M
authors.lastname: König
authors.forename: Kristian
authors.initials: K
authors.lastname: Rother
authors.forename: Michael
authors.initials: M
authors.lastname: Weidlich
authors.forename: Jörn
authors.initials: J
authors.lastname: Behre
authors.forename: Herrmann-Georg
authors.initials: HG
authors.lastname: Holzhütter
mesh_terms: D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology; D006801:Humans
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