lecture recording on 11 March 2025 at 17.04.13 PM

Enzymes and Reactions

• Enzymes: Biological catalysts that speed up reactions by lowering activation energy.

• Substrates: Molecules that undergo a chemical transformation when interacted with an enzyme (e.g., glucose during metabolism).

Specificity of Enzymes

• Specificity: Enzymes are highly specific to their substrates. This specificity prevents inappropriate reactions within the cell.

  • Example: An enzyme breaking down glucose should not act on other molecules.

• Substrates refer specifically to the molecules transformed during reactions catalyzed by enzymes.

• Regulation: Cells can regulate enzyme activity based on environmental conditions, activating or inhibiting enzyme production as necessary.

Importance of Enzymes

• Enzymes are critical for all biochemical processes, catalyzing hundreds to thousands of reactions needed for life.

• Examples include:

  • Synthesis of DNA and RNA

  • Breakdown of food

  • Formation of macromolecules.

Energy and Enzymes

• Energy from Reactions: For example, one mole of sucrose releases sufficient energy (5.64 x 10^3 kJ) during oxidation, yet without enzymes, this reaction could take centuries.

• Enzymes significantly increase the reaction rate, often reducing reaction times to minutes.

• If left alone, substrates (like nucleotides) may take thousands of years to polymerize without enzyme catalysis.

Mechanisms and Naming of Enzymes

• Naming conventions typically follow a systematic format, combining the substrate name with the reaction type plus the suffix "-ase" (e.g., glucose isomerase befitting the isomerization of glucose).

• Exception: Some enzyme names do not follow the typical naming rule (e.g., HIV protease does not derive from a substrate).

Active Sites and Binding

• Active Site: A specific region on the enzyme where substrate binding occurs, often shaped to complement the substrate's structure (lock and key model).

  • Geometric and electronic complementarity are crucial for binding:

    • The active site's shape and charge properties must match those of the substrate.

• Enzymes often make use of chiral specificity, where they can preferentially catalyze one enantiomer over another (important for amino acids).

Catalytic Residues and Mechanisms

• Two types of amino acids in active sites:

  • Residues involved in binding the substrate.

  • Residues involved in catalysis (bond formation/breaking).

• Distinction is important for understanding enzyme function.

Enzyme Strategies for Catalysis

1. Binding Energy: Energy released during substrate-enzyme interactions that helps lower activation energy.

2. Transition State Stabilization: Enzymes stabilize the transition state better than the substrate, thus lowering activation energy (key to facilitating reactions).

3. Acid-Base Catalysis: Side chains in the active site can donate or abstract protons to facilitate the transition state formation.

   • pKa values may shift in the active site environment, altering protonation states.

4. Covalent Catalysis: Formation of a covalent bond between the substrate and the enzyme active site enhances the reaction rate.

5. Metal Ion Catalysis: Metal ions can stabilize charges, activate nucleophiles, or participate in redox reactions, influencing catalysis.

6. Proximity and Orientation Effects: Enzymes arrange substrates in a position and orientation favorable for reaction, which decreases entropy and increases reaction likelihood.

7. Strain: Substrate binding places strain on particular bonds, facilitating their eventual breaking when the reaction occurs.

Example: Carbonic Anhydrase

• Function: Catalyzes the hydration of CO2 to form carbonic acid, essential for blood pH regulation.

• Mechanism involves:

  1. Water interacts with a metal ion (Zn) in the active site, weakening O-H bonds.

  2. Water loses a proton, forming hydroxide, which acts as a nucleophile.

  3. The hydroxide attacks the carbon in CO2, leading to formation of carbonic acid.

• Overall, the enzyme leverages binding energy and stabilizes transition states to facilitate the reaction.