Enzymatic Catalysis Study Notes

  1. Understand the General Properties of Enzymes

  • Enzymes are biological catalysts that accelerate chemical reactions.

  • They achieve this by binding specific substrates and utilizing catalytic chemical groups.

  1. Understand Enzyme Specificity

  • Enzymes are highly specific, catalyzing particular reactions on specific substrates.

  • Stereospecificity: They can distinguish and selectively react with specific stereoisomers.

  1. Can Distinguish Enzyme Cofactors

  • Approximately 1/31/3 of enzymes require metal ions (metalloenzymes) for catalysis (e.g., Fe2+Fe^{2+}, Cu2+Cu^{2+}).

  • Metal ions in catalysis: They bind substrates, mediate oxidation-reduction reactions, and provide electrostatic stabilization.

  • Advantage: Can neutralize charges without altering pH.

  1. Understand Activation Energy, the Reaction Coordinate, and How These Change with Enzymes

  • Enzymes lower the free energy of transition states, increasing reaction rates (reducing the activation energy peak).

  • Preferential Binding of the Transition State: Enzymes bind the transition state more tightly than substrates or products, enhancing reaction rates.

  • Energy Relationship: The activation energy for enzyme-catalyzed processes is lower: △G<em>E‡<△G</em>N‡\triangle G<em>{\text{E}}^{\ddagger} < \triangle G</em>{\text{N}}^{\ddagger}.

  • Rate Enhancement Formula: Rate enhancement=e△△Gcat‡RT\text{Rate enhancement} = e^{\frac{\triangle \triangle G_{\text{cat}}^{\ddagger}}{RT}}.

  • Transition State Analogs: These resemble the transition state and are potent enzyme inhibitors (e.g., ACE inhibitors, HIV-1 protease inhibitors).

  1. Understand Catalytic Mechanisms of Enzymes

  • Key Mechanisms: Acid-base catalysis, covalent catalysis, metal ion catalysis, proximity and orientation effects, preferential binding of the transition state complex.

  • Acid-Base Catalysis: Involves proton transfer (donation by general acid or abstraction by general base) to stabilize the transition state.

    • Catalytic Residues: Asp, Glu, His, Cys, Tyr, Lys side chains.

  • Covalent Catalysis: Transient covalent bond formed between an enzyme's nucleophilic group (e.g., Lys, His, Cys, Ser) and substrate's electrophilic group.

  • Proximity and Orientation Effects: Enzymes bring substrates together, orient them optimally, stabilize transition states via electrostatic effects, and reduce entropy of activation.