Enzymes are macromolecules, usually proteins, produced in living systems, which act as catalysts in physiological reactions. The striking characteristics of enzymes are their catalytic power and specificity. Enzymes have immense catalytic power; they accelerate reactions by factors of at least a million. Most reactions in living systems do not occur at perceptible rates in the absence of enzymes. A simple reaction like hydration of CO2 is catalyzed by the enzyme carbonic anhydrase. The transfer of CO2 from tissues into the blood and then to the alveolar air would be very slow in the absence of this enzyme. The enzyme can hydrate 105 molecules of CO2 per second, which is 107 times faster than the unanalyzed one.
This example illustrates the fact that enzymes have immense catalytic power; enzymes increase rates of reaction by 106 to 1020 times. The catalytic power of proteins comes from their capacity to bind substrates (reactant) molecules in precise orientations and to stabilize transition states in the making and breaking of bonds.
Enzymes are highly specific. An enzyme usually catalyses a single chemical reaction or a set of closely related reactions. For e.g., urease catalyses the hydrolysis of urea only.
Other examples of enzyme catalyzed reactions are as follows:
The remarkable specificity of enzymes comes from the ability of the enzymes to bring the substrates into a favorable orientation in the enzyme-substrate (ES) complexes such that the substrates are bound to specific regions of the enzymes. Each enzyme has a specific active site. The active site of an enzyme binds the substrate and contains the residues that directly participate in the making and breaking of bonds. Some key features of the active site are:
1) The active site takes up a relatively small part of the total volume of an enzyme.
2) The active site is a three dimensional entity formed by groups that come from different parts of the linear amino acid sequence.
3) Enzymes bind the substrate by multiple weak interactions. These weak interactions are electrostatic bonds, hydrogen bonds, van der Waals' forces and hydrophobic interactions. van der Waals' forces become significant in binding only when many substrate species can come simultaneously close to many enzymes species. Hence, the enzyme and substrate should have complementary shapes. The directional nature of hydrogen bonds between substrate and enzyme brings about a high degree of specificity.
4) Active sites are clefts and crevices. Substrate molecules bind to the clefts or crevices.
5) The specificity of binding of a substrate depends on the precise defined arrangement of atoms in the active site. To fit into the active site the substrate must have a matching shape, just like how a key fits into a lock.
fig 7.7 (a) - Lock and Key model of the interaction of substrate and enzyme. The active site of the enzyme alone is complementary in shape to that of the enzyme
This model was proposed in the late 19th century. Since then, modern X-ray crystallographic and spectroscopic methods have revealed that in many cases, enzymes are markedly modified by the binding of substrate. The active sites of these enzymes have shapes that are complementary to that of the substrate only after the substrate is bound. Such enzyme-substrate interaction are described by induced fit model.
fig 7.7 (b) - Induced-fit model of the interaction of substrates and enzymes. The enzyme changes shape upon binding substrate. The active site has a shape complementary to that of the substrate only after the substrate is bound
In enzyme catalyzed reaction, the rate of reaction varies with the concentration of the substrate in the manner as shown in figure.
fig 7.8 - Representation of rate of a enzymes catalyzed with substrate concentration
At a given concentration of enzyme, the rate of reaction is almost linearly proportional to [S] when [S] is low. At high [S], r is nearly independent of [S]. To account for such behavior, Leonor Michaelis and Maud Menten proposed the following steps in enzyme catalyzed reactions.
The formation of ES complex is fast and reversible, while the formation of the product (step 2) is the slow, rate determining step. The rate of enzyme catalyzed reaction changes from first order to zero order as the concentration of the substrate is increased.
