Introduction to Enzymes and Catalysis

Thermodynamics and Enzyme Limits

It is crucial to distinguish between the rate of a reaction and the equilibrium of a reaction. Enzymes are masters of speed, but they are powerless to change the fundamental thermodynamics of a reaction.

The direction and extent of a reaction are determined by the change in Gibbs free energy ($\Delta G$).

1. Exergonic reactions: $\Delta G$ is negative, meaning the reaction occurs spontaneously.
2. Endergonic reactions: $\Delta G$ is positive, meaning the reaction requires an input of energy to proceed.
3. Equilibrium: $\Delta G = 0$, meaning there is no net change in the amounts of reactants or products.

The relationship between the standard free energy change ($\Delta G^{\circ \prime}$) and the equilibrium constant ($K_{\text{eq}}^{\prime}$) at $25^{\circ}\text{C}$ is given by the following equation:

$$\begin{aligned} \Delta G^{\circ \prime} = -RT \ln K_{\text{eq}}^{\prime} \end{aligned}$$

Where $R$ is the gas constant and $T$ is the temperature in Kelvin. Because of this relationship, the more exergonic a reaction is (the more negative the $\Delta G^{\circ \prime}$), the larger the equilibrium constant will be.

Classification of Enzymes

Enzymes are categorized into six major classes based on the type of reaction they catalyze:

• Oxidoreductases: Catalyze oxidation-reduction (redox) reactions, such as lactate dehydrogenase.
• Transferases: Move functional groups from one molecule to another, such as aminotransferases.
• Hydrolases: Cleave chemical bonds through the addition of water. A specific subset of these are proteolytic enzymes, which catalyze the hydrolysis of peptide bonds in proteins.
• Lyases: Remove atoms from substrates to form double bonds or add atoms to existing double bonds, such as fumarase.
• Isomerases: Catalyze structural rearrangements (isomerizations) within a single molecule, such as converting an aldose to a ketose.
• Ligases: Join two large molecules together, a process that requires energy, typically from ATP hydrolysis (e.g., DNA ligase).

Enzyme Composition: Cofactors and Coenzymes

Not all enzymes consist solely of amino acids. Many require non-protein components to function effectively. These helper molecules are called cofactors.

Cofactors can be broadly divided into two categories:

1. Coenzymes: Organic molecules, often derived from vitamins.
2. Metals: Inorganic ions.

The terminology used to describe the enzyme's state depends on whether these cofactors are present:

• Apoenzyme: The protein portion of the enzyme that is inactive without its cofactor.
• Holoenzyme: The complete, catalytically active enzyme consisting of the protein (apoenzyme) plus its required cofactor.
• Prosthetic Group: A specific type of cofactor that is very tightly or even covalently bound to the enzyme.

Exam Tip: Binding Energy Remember that the "driving force" for catalysis is binding energy. This is the free energy released when the enzyme interacts with the substrate. The enzyme achieves its maximum binding energy when it interacts with the transition state, which is what allows it to lower the activation energy so effectively.