Kinetic Modeling of Mithochondral ATP Production

The objectives of this work are to determine the extent to which intracellular metabolite diffusion limits aerobic metabolism and hence dictates cellular dimensions and metabolic organization. The particular focus is on the reaction and diffusion of metabolites that link mitochondria and cellular ATPases, which include ATP, ADP, Pi, arginine phosphate (AP), and arginine in fish and crab muscle as model systems that provide insight into burst swimming muscles. The current work also incorporates oxygen and myoglobin diffusion and reaction and their coupling to the mitochondria. In the first step of model development, an analytical equation for the ATP flux from the mitochondrial inter membrane space was developed from detailed mitochondrial models reported in the literature. This function provides ATP flux from the mitochondria in terms of ADP, Pi, and oxygen concentrations, and it is incorporated within one and two dimensional models of muscle cells. Sensitivity analysis of the mitochondrial model is used to determine the key parameters that affect the kinetics of ATP formation. The second step involves incorporating this analytical function as a boundary condition in a transient spatially dependent diffusion-reaction model of the muscle cell. The full system of partial differential equations are solved with finite element methods and are used to assess the relative effects of diffusion and reaction on overall ATP utilization.