Catalysis
 
 Catalysis by enzymes starts with the collision between the enzyme E and its substrate A to form an enzyme-substrate complex EA: 

This is a second-order reaction, as it involves two reactants, and the collision rate is equal to k[Et] [At], where k is a second-order rate constant. There is a distinct limit to the value of k, as it cannot exceed the diffusion rate. Nonproductive complexes can also form as a result of the interaction of a substrate with an enzyme. If the structure of a substrate is complementary to that of the active site of the enzyme, the interaction rate is high and the binding tight. If, however, this is not the case, some of the binding energy has to be utilized to facilitate the interaction through a conformational change or clamping reaction on the enzyme. Binding is the product of the initial interaction and the subsequent conformational change.
 After being bound to the enzyme, the substrate must undergo activation. That is, a proportion of the total number of substrate molecules in the ground state must be raised to the transition state. This is a short-lived, unstable species with a structure intermediate between that of the substrate and the product. These activated molecules can fall back to the ground state or be converted to EP* at a rate that is independent of the structure of the reactants. The activation energy barrier for the conversion of ground-state molecules to transition-state molecules is very much lower for an enzyme-catalyzed reaction than for either a noncatalyzed reaction or chemically catalyzed reaction. In the activated state, the substrate is bound more tightly to the enzyme than it is in the ground state. If such tighter binding did not occur, there would be no catalysis. In fact, the increase in rate is proportional to the increase in binding. It is for this reason that transition state analogues are potent inhibitors of enzymes. After formation of the EP* complex, the enzyme undergoes another conformational or unclamping reaction to release the product into the bulk medium and regenerate the free form of enzyme. Such regeneration is an essential part of enzymic catalysis.
 
References
1. D. D. Hackney (1990) The Enzymes 19, 1–36.