This page collects and disseminates models of components/pathways of mammalian central metabolism for potential combination into large-scale models. The emphasis of this collection is in energy metabolism in muscle, including models of glycolysis/glycogenolysis, beta-oxidation, the tricarboxylic acid cycle, mitochondrial transporters, and oxidative phosphorylation. Many of the models and model components are built for use with the MATLAB-based Biochemical Simulation Environment (BISEN) for modular construction of metabolic systems models.
Modeling and Simulation Resources
Biochemical Thermodynamics: A Database of biochemical thermodynamic quantities that can be used to obtain formation properties and dissociation constants (provided as pK’s) for reference species associated with biochemical reactants at specified temperature and ionic strength; and to obtain reaction properties (including free energies and enthalpies) for associated reactions of glycolysis, the tricarboxylic Acid Cycle & the pentose phosphate pathway.
BISEN: The BISEN software package is a suite of tools for generating equations and associated computer programs for simulating biochemical systems.
Models of Enzymes and Transporters: This resource provides a set of of mechanistic models of functional components of metabolism to use as building blocks to construct computational models of biological systems.
Integrated Systems Models
Oxidative phosphorylation:The Bazil et al. 2016 model (PMID: 26910433) includes the components of the respiratory chain (Complex I, III, & IV) the F1F0 ATPase, ANT, and phosphate transporter, as well as K+/H+ exchange. The model also accounts for ROS production at Complexes I and III. The model is parameterized against data from rat cardiac mitochondria.
Tricarboxylic acid cycle: The Dasika et al. model includes pyruvate dehydrogenase and the enzymes of the TCA cycle, as well as the mono-, di-, and tricarboxylate exchangers. (The model is integrated with the Bazil et al. model of oxidative phosphorylation.)
Glycolysis/glycogenolysis: The Vinnakota et al. (PMID:16617075) model includes the oxidation of glycogen to pyruvate and lactate. It also includes ATP hydrolysis, as well as the adenylate and creatine kinase reactions. (The model works well for resting conditions for skeletal muscle, but requires some structure changes to effectively simulate exercise conditions.)Tricarboxylic acid cycle: The Dasika et al. model includes pyruvate dehydrogenase and the enzymes of the TCA cycle, as well as the mono-, di-, and tricarboxylate exchangers. (The model is integrated with the Bazil et al. model of oxidative phosphorylation.)
- Vanlier, J, F Wu, F Qi, K C Vinnakota, Y Han, RK Dash, and DA Beard. BISEN: Biochemical simulation environment. Bioinformatics 25:836-837, 2009.
- Bazil JN, KC Vinnakota, DA Beard. Catalytic Coupling of Oxidative Phosphorylation, ATP Demand, and Mitochondrial Reactive Oxygen Species Generation. Biophys J. 110:962-71, 2016.
- Li, X, and DA Beard. A database of thermodynamic properties of the reactions of glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway. Database (Oxford) 2011:bar005