UM Exam 2 Lecture 10: Enzyme Classification and Regulation: GOB Chemistry Study Notes

Enzymes: Biological Catalysts

Definition and Function

Enzymes are biological catalysts composed primarily of proteins (and sometimes RNA) that accelerate chemical reactions in living organisms. Their names typically end in "-ase" and are often derived from the substrate they act upon. Enzymes are essential for metabolic processes, enabling reactions to occur rapidly and efficiently under physiological conditions.

• Substrate: The reactant molecule upon which an enzyme acts.

• Product: The molecule(s) formed as a result of the enzymatic reaction.

• Turnover number: The number of substrate molecules converted to product per unit time by a single enzyme molecule.

• Cofactor: A nonprotein molecule (often a metal ion) required for enzyme activity.

• Coenzyme: An organic cofactor, often derived from vitamins, required for catalysis (especially in redox reactions).

• Apoenzyme: The protein portion of an enzyme, lacking its cofactor/coenzyme.

• Holoenzyme: The catalytically active enzyme, consisting of the apoenzyme plus its cofactor/coenzyme.

• Active site: The region of the enzyme where substrate binding and catalysis occur.

How Enzymes Work

Enzymes speed up reactions by lowering the activation energy required for the reaction to proceed. They do not alter the equilibrium or the overall energy change of the reaction, but they make the process faster and more efficient.

• Proximity effect: Enzymes bring reactants close together.

• Orientation effect: Enzymes position reactants in the optimal orientation for reaction.

• Energy effect: Enzymes induce strain in substrate bonds, lowering activation energy.

• Catalytic effect: Enzymes provide functional groups (acidic, basic, etc.) necessary for catalysis.

Classification of Enzymes

Six Major Classes

Enzymes are classified based on the type of reaction they catalyze. Each class has characteristic reactions and important subclasses.

• Oxidoreductases: Catalyze oxidation-reduction (redox) reactions.

  • Dehydrogenases: Remove hydrogen atoms, often forming double bonds. Require coenzymes like FAD or NAD+.

• Transferases: Transfer functional groups between molecules.

  • Kinases: Transfer phosphoryl groups (–PO32-).

  • Transaminases: Transfer amino groups (–NH3+).

• Hydrolases: Catalyze hydrolysis (splitting with water).

  • Lipases: Hydrolyze ester bonds in lipids.

  • Proteases: Hydrolyze peptide bonds in proteins.

  • Nucleases: Hydrolyze phosphate ester bonds in DNA/RNA.

  • Amylases: Hydrolyze glycosidic bonds in starch.

• Isomerases: Catalyze rearrangement of atoms within a molecule to form isomers.

• Lyases: Catalyze addition/removal of groups to/from double bonds (without hydrolysis or oxidation).

• Ligases: Catalyze joining of two molecules, often coupled with ATP hydrolysis.

Oxidoreductase Example

Alcohol dehydrogenase catalyzes the oxidation of ethanol to acetaldehyde, with NAD+ as a coenzyme:

Transferase Example

Phosphofructokinase transfers a phosphoryl group from ATP to fructose-6-phosphate:

Hydrolase Example

Proteases hydrolyze peptide bonds in polypeptides:

Isomerase Example

Triose phosphate isomerase catalyzes the conversion between dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate:

Lyase Example

Fumarase catalyzes the addition of water to fumarate to form malate:

Ligase Example

Pyruvate carboxylase catalyzes the addition of CO2 to pyruvate, forming oxaloacetate (requires ATP):

Enzyme Specificity

Specific vs. Nonspecific Enzymes

Enzyme specificity refers to the ability of an enzyme to select its substrate(s) and catalyze a particular reaction.

• Highly specific enzymes: Catalyze one type of reaction for a single substrate (e.g., urease hydrolyzes urea).

• Nonspecific enzymes: Catalyze a single reaction for a group of similar substrates (e.g., aminopeptidase releases N-terminal amino acids from polypeptides).

Binding Specificity and Stereochemistry

Enzyme binding specificity depends on the stereochemistry of the substrate. The active site must be chemically compatible with the substrate for effective catalysis.

Models of Enzyme-Substrate Interaction

Lock-and-Key Model

The lock-and-key model proposes that the enzyme's active site is a rigid structure that fits the substrate exactly, like a key fits into a lock.

Induced Fit Model

The induced fit model more accurately describes substrate binding. It states that substrate binding induces a conformational change in the enzyme, optimizing the fit and facilitating catalysis. This model explains how enzymes can accommodate substrates with slight structural differences.

Mechanism of Enzyme Action

Atomic-Level Catalysis (Example: Hydrolase)

Enzymes often use a combination of amino acid residues in their active site to facilitate bond cleavage and formation. For example, hydrolases use a triad of amino acids (Asp, Ser, His) to cleave peptide bonds.

• The substrate binds to a hydrophobic pocket in the enzyme.

• Serine is activated to attack the substrate's amide bond.

• Histidine donates a hydrogen, breaking the bond.

• Water replaces the leaving group, completing hydrolysis.

• The enzyme is recycled for another reaction.

Factors Affecting Enzyme Activity

Substrate Concentration

As substrate concentration increases, the reaction rate increases until it reaches a maximum (saturation point), where all enzyme active sites are occupied.

Enzyme Concentration

With excess substrate, increasing enzyme concentration increases the reaction rate linearly.

Combined Effects

Temperature

Enzyme activity increases with temperature up to an optimum point, after which activity decreases due to denaturation.

pH

Each enzyme has an optimal pH range. Deviations from this range can reduce activity or denature the enzyme.

Summary Table: Enzyme Classes and Subclasses

Class	General Reaction	Key Subclasses
Oxidoreductases	Oxidation-reduction	Dehydrogenases
Transferases	Transfer of functional groups	Kinases, Transaminases
Hydrolases	Hydrolysis	Lipases, Proteases, Nucleases, Amylases
Isomerases	Isomerization	---
Lyases	Add/remove groups to/from double bonds	Decarboxylases, Dehydrases, Deaminases, Synthases
Ligases	Bond formation (ATP hydrolysis)	Synthetases, Carboxylases

Additional info: These notes expand on the lecture outline and textbook references, providing definitions, examples, and visual aids for each enzyme class and regulatory factor. The atomic-level mechanism is included for context but is not required for memorization.