Model number

Dynamics of Muscle Glycogenolysis Modeled with pH Time-Course Computation and pH Dependent Reaction Equilibria and Enzyme Kinetics


 	Cellular metabolites are moieties defined by their specific binding constants to H1, Mg21, 
        and K1 or anions without ligands. As a consequence, every biochemical reaction in the cytoplasm
        has an associated proton stoichiometry that is generally noninteger- and pH-dependent. 
        Therefore, with metabolic flux, pH is altered in a medium with finite buffer capacity.
        Apparent equilibrium constants and maximum enzyme velocities, which are functions of pH, 
        are also altered. We augmented an earlier mathematical model of skeletal muscle glycogenolysis 
        with pH-dependent enzyme kinetics and reaction equilibria to compute the time course of pH changes.
        Analysis shows that kinetics and final equilibrium states of the closed system are highly
        constrained by the pH-dependent parameters. This kinetic model of glycogenolysis, 
        coupled to creatine kinase and adenylate kinase, simulated published experiments made with a 
        cell-free enzyme mixture to reconstitute the network and to synthesize PCr and lactate in vitro. 
        Using the enzyme kinetic and thermodynamic data in the literature, the simulations required minimal
        adjustments of parameters to describe the data. These results show that incorporation of 
        appropriate physical chemistry of the reactions with accurate kinetic modeling gives a reasonable 
        simulation of experimental data and is necessary for a physically correct representation of the 
        metabolic network. The approach is general for modeling metabolic networks beyond the specific
        pathway and conditions presented here.

        Model directly based on: 
        Vinnakota K, Kemp ML, Kushmerick MJ, Dynamics of Muscle Glycogenolysis Modeled with pH Time-Course 
        Computation and pH Dependent Reaction Equilibria and Enzyme Kinetics, Biophy J (91), Aug 2006, p1264-1287


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Key terms
Muscle Glycogenolysis
Enzyme Kinetics
creatine kinase
cellular metabolites
metabolic network
skeletal muscle
adenylate kinase

Please cite in any publication for which this software is used and send one reprint to the address given below:
The National Simulation Resource, Director J. B. Bassingthwaighte, Department of Bioengineering, University of Washington, Seattle WA 98195-5061.

Model development and archiving support at 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.