Regulation of enzyme activity by cyclic phosphorylation-dephosphorylation cascades. Thermodynamic constraints.

The currently accepted model describing regulation of enzyme activity by cyclic phosphorylation-dephosphorylation cascades (Stadtman, E.R. and Chock, P.B. (1978) Curr. Top. Cell. Reg. 13, 53-95) does not take into account the fact that the individual phosphorylation and dephosphorylation reactions are reversible. A modification of the model is described which does take into account the reversible nature of the individual modification and demodification reactions. This model predicts that, if the dephosphorylating enzyme is inactive, the phosphorylation reaction will go to equilibrium, rather than to completion, as predicted by the original model. The new model also makes it possible to take into account factors which change the [ATP]/[ADP] ratio and the equilibrium constant for hydrolysis of the phosphorylated enzyme. These factors define a variable 'window' of thermodynamically allowed values of the ratio of phosphorylated to nonphosphorylated enzyme, which is imposed upon the wider range of kinetically allowed values predicted by the original model.