Enzymes: Biological Catalysts

Definition and Role

Enzymes are biological catalysts—primarily proteins (and some RNA molecules)—that accelerate chemical reactions in living organisms without being consumed in the process. Their names typically end in "-ase" and are often derived from the substrate they act upon.

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

• Product: The molecule(s) produced from the enzymatic reaction.

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

• Cofactor: A nonprotein component (often a metal ion) required for enzyme activity (e.g., Cu2+, Fe2+, Mg2+).

• Coenzyme: An organic cofactor, often derived from vitamins, that assists in enzyme function (e.g., NAD+, FAD).

• Apoenzyme: The protein portion of an enzyme, inactive without its cofactor/coenzyme.

• Holoenzyme: The catalytically active enzyme with its cofactor/coenzyme bound.

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

How Enzymes Work

Catalytic Mechanisms

Enzymes speed up reactions by lowering the activation energy required for the reaction to proceed. They do not alter the overall free energy change (ΔG) of the reaction.

• Proximity effect: Enzymes bring reactants close together to increase the likelihood of collision.

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

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

• Catalytic effect: Enzymes provide functional groups (acidic, basic, etc.) that participate in the reaction mechanism.

Classification of Enzymes

The Six Major Classes

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

Oxidoreductases

• Catalyze oxidation-reduction reactions.

• Subclasses: Dehydrogenases (remove 2 H atoms, require NAD+ or FAD as coenzyme).

• General rules:

  • Oxidation: loss of electrons, loss of H, gain of O, acts as reducing agent.

  • Reduction: gain of electrons, gain of H, loss of O, acts as oxidizing agent.

Transferases

• Catalyze transfer of functional groups (e.g., amino, phosphoryl) between molecules.

• Subclasses: Kinases (transfer phosphoryl groups), Transaminases (transfer amino groups).

Hydrolases

• Catalyze hydrolysis reactions (breaking bonds with water).

• Subclasses:

  • Lipases: Hydrolyze ester bonds in lipids.

  • Proteases: Hydrolyze peptide bonds in proteins.

  • Nucleases: Hydrolyze phosphate ester bonds in nucleic acids.

  • Amylases: Hydrolyze glycosidic bonds in starch.

Isomerases

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

Lyases

• Catalyze addition or removal of small molecules to/from double bonds.

• Subclasses: Decarboxylases, Dehydrases, Deaminases, Synthases.

Ligases

• Catalyze the joining of two molecules using energy from ATP hydrolysis.

• Subclasses: Synthetases, Carboxylases.

Enzyme Specificity

Specific vs. Nonspecific Enzymes

Enzyme specificity refers to the ability of an enzyme to select and catalyze a particular reaction for a specific substrate.

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

• Nonspecific enzymes: Catalyze a single reaction for a group of similar substrates (e.g., aminopeptidase acts on various polypeptides).

Models of Enzyme-Substrate Binding

Lock-and-Key vs. Induced Fit Model

• Lock-and-Key Model: The enzyme's active site is a perfect fit for the substrate, like a key in a lock.

• Induced Fit Model: Substrate binding induces a conformational change in the enzyme, optimizing the fit and facilitating catalysis. This model better explains enzyme flexibility and specificity.

Mechanism of Enzyme Action (Example: Serine Protease)

Stepwise Catalysis (Do Not Memorize Details)

Enzymes often use a series of coordinated steps involving amino acid side chains and cofactors to catalyze reactions. For example, serine proteases use a catalytic triad (Ser, His, Asp) to hydrolyze peptide bonds.

Additional info: The enzyme is regenerated at the end of the reaction, ready to catalyze another cycle.

Factors Affecting Enzyme Activity

Substrate Concentration

• At low substrate concentrations, the reaction rate increases linearly with substrate concentration.

• At high substrate concentrations, the rate approaches a maximum (Vmax) as the enzyme becomes saturated.

Enzyme Concentration

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

Temperature

• Reaction rate increases with temperature up to an optimum (usually around 37°C for human enzymes).

• Above the optimum, enzymes denature and activity decreases sharply.

pH

• Each enzyme has an optimum pH at which it is most active.

• Activity decreases at pH values above or below the optimum due to denaturation or altered ionization of active site residues.

Summary Table: Enzyme Classes and Subclasses