8.1 A Few Basic Catalytic Strategies Are Used by Many Enzymes

As we will see in our study of biochemistry, enzymes catalyze a vast array of chemical reactions. Despite this diversity, all enzymes operate by facilitating the formation of the transition state. How the transition state is formed varies from enzyme to enzyme, but most enzymes commonly employ one or more of the following strategies to catalyze specific reactions:

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DID YOU KNOW?

A nucleophile is a chemical that is attracted to regions of positive charge in another molecule. A nucleophile participates in a chemical reaction by donating electrons to another chemical, called the electrophile.

  1. Covalent Catalysis. In covalent catalysis, the active site contains a reactive group, usually a powerful nucleophile that becomes temporarily covalently modified in the course of catalysis. The proteolytic enzyme chymotrypsin provides an excellent example of this mechanism.

  2. General Acid–Base Catalysis. In general acid–base catalysis, a molecule other than water plays the role of a proton donor or acceptor. Chymotrypsin uses a histidine residue as a base catalyst to enhance the nucleophilic power of serine.

  3. Metal Ion Catalysis. Metal ions can function catalytically in several ways. For instance, a metal ion may serve as an electrophilic catalyst, stabilizing a negative charge on a reaction intermediate. Alternatively, a metal ion may generate a nucleophile by increasing the acidity of a nearby molecule, such as water. Finally, a metal ion may bind to the substrate, increasing the number of interactions with the enzyme and thus the binding energy. Metal ions are required cofactors for many of the enzymes that we will encounter in our study of biochemistry.

  4. Catalysis by Approximation and Orientation. Many reactions include two distinct substrates. In such cases, the reaction rate may be considerably enhanced by bringing the two substrates into proximity and in the proper orientation on a single binding surface of an enzyme.

DID YOU KNOW?

An electrophile is a chemical that is electron deficient. Electrophiles are thus attracted to nucleophiles—electron-rich molecules or regions of molecules.

Recall from Chapter 6 our consideration of another key aspect of enzyme catalysis—binding energy. The full complement of binding interactions between an enzyme and a substrate is formed only when the substrate is in the transition state. The fact that binding energy is maximal when the enzyme binds to the transition state favors the formation of the transition state and thereby promotes catalysis.