Search

A computer program is described that derives the Flux and Concentration Control Coefficients for linear and branched metabolic pathways. The program prompts the user to enter a concise description of the metabolic pathway. From this description, the program constructs the appropriate equations in matrix form. The algorithm employed to obtain the symbolic determinants is described, and this algorithm also provides a convenient method for manual derivation of the Control Coefficients. The computer-based method will accommodate unlimited feed-forward and feed-backward loops and a maximum of two branches from each metabolite on the main pathway. The utility of the method is illustrated with a linear path with feed-forward and feed-backward loops, and with a substrate cycle as an example of a path with two branches.

The effect of product inhibition in metabolic pathways is examined using (a) an unbranched pathway in the absence of endproduct inhibition and (b) an unbranched pathway with endproduct inhibition. It is shown that product inhibition may be considered an alternative mechanism to endproduct inhibition for reducing the overall logarithmic gain of an unregulated pathway. When product inhibition and endproduct inhibition are both present, they act in concert with each other to lower the overall logarithmic gain and alleviate parameter sensitivities. Product inhibition is also found to exert a stabilizing influence that competes with the destabilizing effect of endproduct inhibition in controlling the dynamic behavior.