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PMID: 20823849 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology.

Molecular systems biology ·Vol. 6 ·2010-09-07 ·Pages 411

Gille C, Bölling C, Hoppe A, Bulik S, Hoffmann S, Hübner K, Karlstädt A, Ganeshan R, König M, Rother K, Weidlich M, Behre J, Holzhütter HG

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.

MeSH Terms
Hepatocytes/metabolism,physiology Humans
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Gille Christoph
Institute of Biochemistry, University Medicine Charité Berlin, Berlin, Germany.
Bölling Christian
Hoppe Andreas
Bulik Sascha
Hoffmann Sabrina
Hübner Katrin
Karlstädt Anja
Ganeshan Ramanan
König Matthias
Rother Kristian
Weidlich Michael
Behre Jörn
Holzhütter Herrmann-Georg
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Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
DOI
10.1038/msb.2010.62
Published
2010-09-07
Pages
411
Language
English
Region
England
NLM ID
101235389
PMCID
PMC2964118
Subset
IM
External Links
PubMed source DOI: 10.1038/msb.2010.62 PMC Full Text View journal details
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