Enzyme

Consider the simple, uncatalyzed chemical reaction reactant A product B.

As the concentration of reactant A is increased, the rate of product B formation increases. Rate of reaction is defined as the number of molecules of B formed per unit time. In the presence of a catalyst, the reaction rate is accelerated. For reactant to be converted to product, a thermodynamic energy barrier must be overcome. This energy barrier is known as the activation energy (E_a ). A catalyst speeds up a chemical process by lowering the activation energy which the reactant must reach before being converted to product. It does this by allowing a different chemical mechanism or pathway which has a lower activation energy (Fig. 4).

Enzymes have high catalytic power, high substrate specificity, and are generally most active in aqueous solvents at mild temperature and physiological pH. There Figure 3. Illustration by Hans & Cassidy. Courtesy of Gale Group. are thousands of known enzymes, but nearly all can be categorized according to their biological activities into six major classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Most enzymes catalyze the transfer of electrons, atoms, or groups of atoms, and are assigned names according to the type of reaction.

Thousands of enzymes have been discovered and purified to date. The structure, chemical function, and mechanism of hundreds of enzymes has given biochemists a solid understanding of how they work. In the 1930s, J. B. S. Haldane (1892-1964) described the principle that interactions between the enzyme and its substrate can be used to distort the shape of the substrate and induce a chemical reaction. The energy released and used to lower activation energies from the enzyme-substrate interaction is called the binding energy. The chemical form of the substrate at the top of the energy barrier is called a transition state. The maximum number of weak enzyme-substrate interactions is attained when the substrate reaches its transition state. Enzymes stabilize the transition state, allowing the reaction to proceed in the forward direction. The rate-determining process of a simple enzyme catalyzed reaction is the breakdown of the activated complex between the transition state and the enzyme. In 1889 the Swedish chemist Svante Arrhenius (1859-1927) showed the dependence of the rate of reaction on the magnitude of the energy barrier (activation energy). Reactions which consist of several chemical steps will have multiple activated complexes. The over-all rate of the reaction will be determined by the slowest activated complex decomposition. This is called the rate-limiting step.

In addition to enhancing the reaction rate, enzymes have the ability to discriminate among competing substrates. Figure 4. Illustration by Hans & Cassidy. Courtesy of Gale Group. Enzyme specificity arises mainly from three sources: (1) Exclusion of other molecules from the active site because of the presence of incorrect functional groups, or the absence of necessary binding groups. (2) Many weak interactions between the substrate and the enzyme. It is known that the requirement for many interactions is one reason enzymes are very large compared to the substrate. The noncovalent interactions which bind molecules to enzymes are similar to the intramolecular forces which control enzyme conformation. Induced conformational changes shift important chemical groups on the enzyme into close proximity for catalysis. (3) Stereospecificity arises from the fact that enzymes are built from only L-amino acids. They have active sites which are asymmetric and will bind only certain substrates.