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wu_2007

Computer Modeling of Mitochondrial Tricarboxylic Acid Cycle, Oxidative Phosphorylation, Metabolite Transport, and Electrophysiology.

Model number: 0347

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Description

  ABSTRACT: A computational model of mitochondrial metabolism
  and electrophysiology is introduced and applied to analysis
  of data from isolated cardiac mitochondria and data on phosphate
  metabolites in striated muscle in vivo. This model is constructed
  based on detailed kinetics and thermodynamically balanced reaction
  mechanisms and a strict accounting of rapidly equilibrating
  biochemical species. Since building such a model requires introducing
  a large number of adjustable kinetic parameters, a correspondingly
  large amount of independent data from isolated mitochondria
  respiring on different substrates and subject to a variety of
  protocols is used to parameterize the model and ensure that
  it is challenged by a wide range of data corresponding to diverse
  conditions. The developed model is further validated by both
  in vitro data on isolated cardiac mitochondria and in vivo experimental
  measurements on human skeletal muscle. The validated model is
  used to predict the roles of NAD and ADP in regulating the tricarboxylic
  acid cycle dehydrogenase fluxes, demonstrating that NAD is the
  more important regulator. Further model predictions reveal that
  a decrease of cytosolic pH value results in decreases in mitochondrial
  membrane potential and a corresponding drop in the ability of
  the mitochondria to synthesize ATP at the hydrolysis potential
  required for cellular function.
  
  The original paper reference is cited below:
  
  Computer Modeling of Mitochondrial Tricarboxylic Acid Cycle,
  Oxidative Phosphorylation, Metabolite Transport, and Electrophysiology,
  Fan Wu, Feng Yang, Kalyan C. Vinnakota, Daniel A. Beard, 2007,
  Journal of Biological Chemistry, volume 282, PubMed ID: 17591785
 	



Above figure taken directly from Wu et al. 2007 paper.

Equations

The equations for this model may be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.

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References

   Fan Wu, Feng Yang, Kalyan C. Vinnakota, Daniel A. Beard, Computer Modeling of 
   Mitochondrial Tricarboxylic Acid Cycle, Oxidative Phosphorylation, Metabolite Transport, 
   and Electrophysiology, 2007, J of Biological Chem, vol 282. PMID: 17591785	

   LaNoue, K., Nicklas, W. J., and Williamson, J. R. (1970) J. Biol. Chem. 245, 102–111

   Bose, S., French, S., Evans, F. J., Joubert, F., and Balaban, R. S. (2003) J. Biol.
   Chem. 278, 39155–39165

   Orig CellML model: www.models.cellml.org/exposure/357bde3407ba7c30baafce4903674d97

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Key Terms

Mitochondria, Metabolism, Publication, Data, Electrophsyiology, NAD, ADP, TCA cycle, transport, enzyme reaction, redox, matlab, cellml

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Acknowledgements

Please cite www.physiome.org in any publication for which this software is used and send an email with the citation and, if possible, a PDF file of the paper to: staff@physiome.org.
Or send a copy to:
The National Simulation Resource, Director J. B. Bassingthwaighte, Department of Bioengineering, University of Washington, Seattle WA 98195-5061.

[This page was last modified 29Jan20, 1:02 pm.]

Model development and archiving support at physiome.org provided by the following grants: NIH U01HL122199 Analyzing the Cardiac Power Grid, 09/15/2015 - 05/31/2020, NIH/NIBIB BE08407 Software Integration, JSim and SBW 6/1/09-5/31/13; NIH/NHLBI T15 HL88516-01 Modeling for Heart, Lung and Blood: From Cell to Organ, 4/1/07-3/31/11; NSF BES-0506477 Adaptive Multi-Scale Model Simulation, 8/15/05-7/31/08; NIH/NHLBI R01 HL073598 Core 3: 3D Imaging and Computer Modeling of the Respiratory Tract, 9/1/04-8/31/09; as well as prior support from NIH/NCRR P41 RR01243 Simulation Resource in Circulatory Mass Transport and Exchange, 12/1/1980-11/30/01 and NIH/NIBIB R01 EB001973 JSim: A Simulation Analysis Platform, 3/1/02-2/28/07.