Determining the transient kinetic behavior of complex multi-enzyme systems by use of network thermodynamics.

As an example of the application of network thermodynamics to the treatment of complicated enzymatic systems, we have studied the transient kinetic behavior of a sequence of five enzymatic reactions, four with Michaelis-Menten kinetics and the final one with sigmoid kinetics. The object was to determine how the time-courses of the concentrations of all the intermediate substrates involved, depend on the effect of forward activation by the first substrate on the final enzymatic step. The case with forward activation exhibited an unexpected behavior with a reversal of the direction of the reaction before reaching equilibrium. The solution of the set of five non-linear differential equations was achieved using the student version of the simulation package PSPICE. The same approach can be utilized to study the behavior of any type of complex multienzymatic system (steady-states, transients, oscillations, chaos), or of combinations of enzymatic reactions with transmembrane transport in compartmental systems.