Enzymes as biosensors. 1. Enzyme memory and sensing chemical signals

When a free enzyme exists under different conformations that 'slowly' isomerize during the conversion of a substrate into a product, the corresponding 'slow' relaxation component may interfere with the steady-state component. The apparent steady-state rate that may be measured under these conditions is called the meta-steady-state rate for it refers to the existence of metastable states of the enzyme during the reaction. By contrast to the real steady-state rate, the meta-steady-state rate is dependent upon the initial state of the enzyme, that is on the respective concentrations of the free enzyme forms. The simplest model that may display this type of behaviour is the mnemonical model. For a fixed concentration of the last product of the reaction sequence the meta-steady state is different depending on that concentration being reached by an increase or a decrease of a previous concentration. This means that the meta-steady-state rate describes a hysteresis loop as the product concentration is increased and decreased. Owing to the existence of metastable states, the enzyme system behaves as a biosensor that is able to detect both a concentration and the direction of a concentration change. The existence of the hysteresis loop of the meta-steady-state rate implies that the two free enzyme forms display hysteresis as well. A chemical potential, called the sensing potential, is specifically associated with the 'perception' of the direction of the thermodynamic force generated by the decrease or the increase of the concentration of the ligand that binds to one of the enzyme conformations. The sensing potential of the enzyme conformer that does not bind the product increases and reaches a plateau as the chemical potential of that product is raised. Alternatively the sensing potential of the other conformer vanishes at low and high chemical potentials of the product and is significant for intermediate chemical potentials. Enzymes that display very slow conformation changes may thus be viewed as elementary sensor devices.