Simulation of the Purine Nucleotide Cycle As an Anaplerotic Process in Skeletal Muscle

A computer model of purine nucleotide and citric acid cycles joined through fumarate is given. Steady-state equations corresponding to metabolic enzymes are written based on the information from the literature about their kinetic behavior. Numerical integration of this set of equations is performed and in order to maintain an overall stabilization between the two cycles, enzymatic activities, in the form of V, have been calculated. Sensitivity coefficients for enzymes indicate that the control is exerted, depending upon the intermediate concentrations, and furthermore, it is demonstrated that AMP concentration in muscle should be very low. From stabilization, simulation of exercise conditions has been performed by diminishing [ATP] and increasing accordingly [ADP] and [AMP]. In such conditions the operation of purine nucleotide cycle leads to a considerable increase in the level of citric acid cycle intermediates. Disruption of purine nucleotide cycle by altering some of the three enzymatic steps leads to a lesser increase of these intermediates. The set of results presented seems to confirm the hypothesis that purine nucleotide cycle acts as an anaplerotic process in muscle, as the experimental results of Aragon and Lowenstein (Aragon, J.J., and Lowenstein, J.M. (1980) Eur. J. Biochem. 110, 371-377) suggest.