Theory of Enzyme Catalysis

Enzymes are often considered to function by general acid-base catalysis or by covalent catalysis, but these considerations alone cannot account for the high efficiency of enzymes. Proximity and orientation effects may be partially responsible for the discrepancy, but even the inclusion of these effects does not resolve the disparity between observed and theoretically predicted rates. These and other aspects of the theories of enzyme catalysis are treated in the monographs by Jencks (33) and Bender (34). 

O. Tapia, Beyond standard quantum chemical semi-classic approaches Towards a quantum theory of enzyme catalysis, in P. Paneth, A. Dybala-Defratyka (Eds.), Kinetics and Dynamics, From nano- to bio-scale, Challenges and advances in computational chemistry and physics 12, Springer Science, Dordrecht, 2010, p. 267-298. 

In this section the basic kinetic model for enzyme-catalyzed bioconversions is presented. Understanding this model is the foundation for deriving more complex models. In their theory of enzyme catalysis, Michaelis and Menten 113 postulated the existence of an enzyme substrate complex (ES), which is built up in a reversible... 

An enzyme is typically a large protein molecule that contains one or more active sites where interactions with substrates take place. These sites are structurally compatible with specific substrate molecules, in much the same way as a key fits a particular lock. In fact, the notion of a rigid enzyme structure that binds only to molecules whose shape exactly matches that of the active site was the basis of an early theory of enzyme catalysis, the so-called lock-and-key theory developed by the German chemist Emil Eischer in 1894 (Eigure 13.25). Eischer s hypothesis accounts for the specificity... 

According to the most advanced theories of enzyme catalysis, differential stabilisation of reaction transition states relative to ground states is the most effective way to effect catalysis irrespective of whether there is an excess or lack of substrate available for biocatalysis (see Chapter 8 Figure 10.17). Therefore, in order for an antibody to act as an enzyme, the antibody... 

The first notion on the deviation of elementary catalytic acts of enzyme reaction, from that prescribed by classical thermodynamic and kinetic approaches, was, probably, formulated in 1971 [19]. It had been shown that the application of basic postulates of activated state theory to the majority of enzyme processes can lead to physically meaningless values of the activation parameters (energy and entropy of activation). It was emphasized that enzyme functioning is more similar to the work of a mechanical construction than to the catalytic homogeneous chemical reaction. The selfconsistent phenomenological relaxation theory of enzyme catalysis was proposed in 1972 [20, 21]. 

As noted previously, noncovalent association between the enzyme and its substrate(s) is the essential first step in biocatalytic reactions. Although early theories of enzyme catalysis focused primarily on interactions between the enzyme and substtate, it was later appredated that maximizing selective, noncovalent interactions between the enzyme and the high-energy uansition state(s) that linked enzyme-bound complexes of substrates and products was the key to efficient rate enhancements. A somewhat oversimplified view is that ground-state interactions determine substrate specifidty and transition-state interactions yield rate enhancements. 

Cook, D.B., McKenna, J. Contribution to the theory of enzyme catalysis potential importance of vibrational activation entropy. J. Chem. Soc. Perkin Trans. 2.1974, 1223-1225. 

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