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A Kinetic Reaction Network Model for Energetic Metabolism in Rat Hepatocytes
Author(s) -
Yang Feng,
Beard Daniel A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1300-a
A computational model describing hepatocyte energy metabolism is presented and parameterized based on a published data set of metabolic fluxes and substrate concentrations in perfused liver. This analysis integrates previously developed models of oxidative phosphorylation, tricarboxylic acid cycle, glycogenolysis and glycolysis. In addition, a kinetic model for cytosolic NADPH‐dependent and microsomal NAD(P)H‐dependent reactive oxygen species (ROS) production is also included to study the development of oxidative stress in liver. Flux expressions for biochemical reactions involving proton stoichiometry, and reactants that reversibly bind hydrogen ion, are modified to account for pH variation. The identified model is then validated by comparison to data from independent experiments. The constructed model can be used for simulating the metabolism and regulation in the liver cell in different situations, and will be used as a platform for modeling drug metabolism and drug‐drug metabolic interaction in liver. This work was supported by NIH grant GM068610.