Chemical Basis for Enzyme Action

It is clear that the formation of an enzyme-substrate complex is required for both the catalytic action of an enzyme and its substrate specificity. Substrates are bound to a relatively small region of the enzyme called the active or catalytic site, which contains specific residues directly responsible for catalytic action. The active site is three-dimensional and is formed by groups from different areas of the linear polypeptide sequence. Activity therefore depends on the integrity of the three-dimensional structure of the enzyme. The specificity of binding depends upon a complementary relationship between the enzyme active site and the substrate. 

There are several processes that account for the enhancement of reaction rates by enzymes. The major mechanisms are proximity-entropy effects, substrate strain, covalent catalysis, and acid-base catalysis. 

Many enzymes form covalent bonds with their substrates to form true intermediates. Enzyme-bound coenzymes (prosthetic groups) can also form covalent bonds with the substrate. Enzyme effects involving such formation of covalent bonds with the substrate are referred to as covalent catalysis. The enzyme-bound or coenzyme-bound substrate is more reactive than the original substrate. An example is transamination (Chapter 20), where the amino acid 

The pK of the histidine imidazole residue is about 6.0. At or near this pH, the rates of protonation and deprotonation are not only equal but also very rapid. Such a mechanism probably increases reaction rates by lO lO3- 

In many cases, a combination of mechanisms will exist, proximity-entropy effects, covalent modification, and general acid-base effects as well as other processes that we may not have discussed. 

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