Earlier Theories of Enzyme Catalysis

The most simple general picture of enzyme catalysis is given by the scheme proposed by Michaelis and Menten 

Analyzing existing theoretical approaches to explain the mechanism of enzyme functioning, we can conclude that all points of view concerning the origin of the extremely high catalytic activity of enzymes may be subdivided into four groups. 

The first two explanations are the natural consequences of classical kinetics. According to transition-state theory, as generally accepted by biochemists, the value of a rate constant, k = k T/h)exp SJR)exp —EJRT), is determined by two main exponentially dependent factors. The rate constant can be increased either by increasing activation entropy or by decreasing activation energy. 

Let us start our analysis with consideration of the first factor, i.e., with the entropic explanation of enzyme activity. This approach has been used by Koshland to describe those kinds of processes that, when drawing together substrate molecules, ions and substrates, cofactors and substrates, etc., are the obligatory intermediary steps determining the overall reaction rate [7,8]. In the frame of the transition state theory, the configuration of the activated complex, that corresponds to the lowest potential barrier, is reached with the precise position and mutual orientation of the reactants. This means that such ordering of the reagents, in the course of an activated complex formation, would be accompanied by the initial entropy decrease, i.e., by the positive contribution to the activation entropy, S, of a model system. 

Milstein and Cohen [9] tried to verify experimentally Koshland s approach by comparing the rates of two kinds of chemical processes  

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