Types of Enzyme Catalysis

Here are the 5 main types of catalytic mechanisms employed by enzymes:

1. Acid/Base Catalysis
2. Covalent Catalysis
3. Metal Ion Catalysis
4. Proximity and Orientation Effects
5. Preferential binding of the transition state complex

Acid/Base Catalysis:

• Here the enzyme protonates or deprotonates the substrate to lower the free energy of the transition state.
  • The enzyme can either act as an acid or base

• Examples of Acid/Base Catalysis
  • RNAase A
    • A hydrolase that hydrolyzes phosphodiester bonds in RNA
    • Active sites has two Histidines
    • Involves a 2^‘3^‘ cyclic nucleotide intermediate
    • Mostly beta sheet
    • His 12 acts as a general base and His 119 as a general acid to promote nucleophilic attack and bond cleavage.

Covalent Catalysis:

• A catalytic mechanism that involved an enzyme-substrate covalent intermediate
• Transient formation of the complex increases reaction rates
• The enzyme nucleophilically attacks the substrate (also called nucleophilic catalysis)
• Reversible

Metal Ion Catalysis:

Catalysis involving a metal ion can occur via several different mechanisms:

• Coordinate substrates and orient them properly
• Mediate redox reactions by acting as electron donor or acceptor
• Stabilize or shield negatively charges species (usually to allow nucleophile to enter)
• Make coordinated waters more acidic (better nucleophile

Example: Carbonic Anhydrase

• Requires Zn2+ which is coordinated by 3 His and 1 H2O

Proximity/Orientation:

• Enzymes bring substrates into contact with catalytic groups
• Restricts rotational and translational motion of substrated when bound
• Can increase reaction rates by 10⁷

Preferential Transition State Binding:

• Reaction rates increase by increasing the concentration of the transition state
• Some enzymes bind tighter to the T.S. than to the substrate
• Binding substrate force it to adopt the T.S. by straining the molecule towards that molecule.
• T.S. analogs will be potent inhibitors of these enzymes