pH‐induced co‐operative effects in hysteretic enzymes

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Abstract
A new model which provides an explanation for pH‐induced co‐operativity of hysteretic enzymes is proposed. The essence of the model is that a region, or a domain, of the enzyme undergoes a spontaneous ‘slow’ conformational change which does not affect the geometry of the active site. The region which undergoes this spontaneous conformational transition bears an ionizable group. Kinetic co‐operativity occurs if the pK of this ionizable group changes upon this conformational transition. Thus co‐operativity does not arise from a distortion of the active site.An interesting prediction of the model is that at ‘extreme’ pH values co‐operativity must be suppressed. Although the kinetic equation pertaining to the model is of the 2:2 type, co‐operativity is not maximum or minimum at half‐saturation of the enzyme by the substrate, as occurs with 2:2 binding isotherms. A new index of maximum or minimum kinetic co‐operativity, whether this extreme occurs at half‐saturation or not, has been proposed which allows the change of kinetic co‐operativity to be followed as a function of pH.It is believed that this model will be useful in explaining the behaviour of enzymes attached to biological polyelectrolytes, such as membranes or cell envelopes.