MECHANISMS OF ENZYMATIC REACTIONS - New Trends in Enzyme Catalysis and Biomimetic Chemical Reactions - page 35

CHAPTER 2

MECHANISMS OF ENZYMATIC REACTIONS

2.1. General principles of enzymatic catalysis

Creating enzymes in the processes of biological evolution, Nature used a whole arsenal of
mechanisms of chemical reactions including covalent catalysis, general acid/base catalysis,
electrostatic catalysis, desolvation, strain or distortion, short- and long-distance electron
transfer, proton and hydride transfer, multielectron transfer, synchronous reactions, and
donor-acceptor catalysis. Specific forces maintaining the enzyme's native structure and
providing its interaction with substrates and inhibitors are similar to those we meet in
chemistry. They are covalent bonds, ionic (electrostatic) interactions, ion-dipoles and
dipole-dipole interactions, hydrogen bonds, charge transfer complexes, hydrophobic
interactions, and van der Waals Forces.
A large group of scientists, including the author, believe that a chemical catalytic
process, as well as an enzymatic reaction contains a certain sequence of elementary
chemical steps. Each of these steps proceeds by “ordinary” laws of chemical kinetics. The
accelerating action of a catalyst is accounted for by the fact that its active centers become
involved in such chemical reactions with substrate molecules, which lead to an increase in
the velocity of the process as a whole. Within the framework of this concept, enzymes are
characterized by a set of certain specific properties, which have been “polished off “in the
course of biological evolution.
According to modern concepts, the occurrence of a catalytic reaction proceeds at a
sufficient rate provided the following factors (“selection” rules) are operating in concert:
The Thermodynamic Feasibility of the Process as a Whole. The change of the
positive standard Gibbs energy

1.

in an each step must not be greater than about 20-30

kJ/mole.

2.

Proximity and Orientation Effects of the Substrate Molecules and the Catalytic Site.
The preliminary approach of two reacting particles during a complex catalyst-substrate
formation, resulting from the interaction of the groups that do not participate directly in
subsequent chemical reactions (binding groups), increases the rate constant of the reaction
by about times. The precise orientation of the substrate relative to catalytic groups may
provide an additional acceleration of to times, depending on the type of reactions.
For reactions involving three and more molecules, the acceleration due to these effects
may be considerably greater. The proximity and precise orientation prevents a loss of
entropy converting a multimolecular reaction to a monomolecular one.
Low Energy Activation in Each Step. In certain cases, the rule is, the better the
thermodynamic of the step, the lower the energy activation (Polanyi-Semenov, Bronsted
equations, for example).

3.

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