13.1 Introduction
Enzymes are proteins that catalyze body’s chemical reactions. They can increase the rate of reaction as much 106 by reducing the activation energy without affecting the equilibrium. Since the enzymes are proteins, they are made up of amino acids linked together by peptide bonds. The reactant of an enzyme-catalyzed reaction is called as substrate (Figure 1). The specificity of the enzyme for its substrate is known as molecular recognition.
Figure 1. Enzyme-catalyzed reactions.
13. 2 Active Site
Active site of an enzyme is generally a hollow on the protein surface where the substrate can bind (Figure 2). The substrate is generally bound to amino acids present in the binding site by
Figure 2
variety of interactions such as van der Waals interaction, H-bonding and ionic bonding. These interactions are to strong enough to hold the substrate for the reaction to take place, but weak enough to allow the product to depart once it is produced.
The amino acids present in the active site also assist in the reaction mechanism. For example, nucleophilic amino acid such as serine is commonly involved in enzyme-catalyzed reaction mechanisms and will form covalent bond with the substrate as part of the reaction mechanism (Figure 3).
Figure 3
13.3 Acetylcholine Hydrolysis
There are many reasons why enzymes catalyze the reactions. In figure 3 we have seen an example where amino acid in the active site can assist the enzyme mechanism acting as a nucleophile. Another reason why enzyme acts as catalyst is the binding process itself. The active site is not ideal shape for the substrate, but when the binding takes place the shape changes to accommodate the substrate and maximizes the possible interactions of the substrate with amino acids of the active site. This is called as an induced fit (Figure 4).
Figure 4. Induced fit
These binding process also force the substrate to adopt a specific conformation which is ideal for the reaction with nucleophile and catalytic amino acids. Furthermore, the binding between the substrate and enzyme is that important bonds in the substrate may be strained and weakened, allowing the reaction takes place more easily. For an example, neurotransmitter acetylcholine is hydrolyzed by the enzyme acetylcholinesterase (Scheme 1). In this process, acetylcholine is bound in the active site such that it is held in position to undergo reaction with nucleophilic serine OH group. A histidine residue is also position such a way to act as an acid/base catalyst. H-Bonding between the ester group of the substrate with a tyrosine residue in the active site also aids to weaken the ester linkage, allowing it to be cleaved more easily.
Scheme 1. Acetylcholine hydrolysis