A model for the mitochondrial respiratory chain that appropriately balances mass, charge, and free energy transduction and analyzed based on a previously published set of data measured on isolated cardiac mitochondria.

Description

   A computational model for the mitochondrial respiratory chain that appropriately 
   balances mass, charge, and free energy transduction is introduced and analyzed based 
   on a previously published set of data measured on isolated cardiac mitochondria. 
   The basic components included in the model are the reactions at complexes I, III, and
   IV of the electron transport system, ATP synthesis at F1F0 ATPase, substrate 
   transporters including adenine nucleotide translocase and the phosphate\hydrogen 
   co-transporter, and cation fluxes across the inner membrane including fluxes through 
   the K+/H+ antiporter and passive H+ and K+ permeation. Estimation of 16 adjustable 
   parameter values is based on fitting model simulations to nine independent data 
   curves. The identified model is further validated by comparison to additional datasets m
   easured from mitochondria isolated from rat heart and liver and observed at low 
   oxygen concentration. To obtain reasonable fits to the available data, it is necessary 
   to incorporate inorganic-phosphate-dependent activation of the dehydrogenase activity 
   and the electron transport system. Specifically, it is shown that a model incorporating 
   phosphate-dependent activation of complex III is able to reasonably reproduce the 
   observed data. The resulting validated and verified model provides a foundation for 
   building larger and more complex systems models and investigating complex physiological 
   and pathophysiological interactions in cardiac energetics. 

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.