Some of the contributors to these rate enhancements are:

• Acid-Base Catalysis: acidic and basic groups in amino acid side chains can serve as proton transfer agents

• Electrostatic Catalysis: charged side chains can stabilize intermediates of the opposite charge;
  • For example, a carboxylate anion can stabilize a carbocation intermediate,

  • A positive metal ion can stabilize a negative oxyanion; could also be described as electrohilic catalysis

• Nucleophilic Catalysis: a nucleophile from the enzyme, such as a serine OH, can displace the leaving group in a substrate, forming an intermediate that is more reactive than the initial substrate; this is how serine peptidases function

• Transition State Stabilization: many enzymes bind the transition states (TS) of the reactions they catalyze more tightly than they bind the substrate
  • This facilitates the formation of the TS - a notion originally suggested by Linus Pauling.

  • Transition state stabilization may take two forms:
    • the shape of the active site may be a closer match for the TS than for the substrate

    • polar residues might bind more tightly to the partial charges in the TS; alternatively, if charge decreases on passing to the TS, lipophilic residues might stabilize it

  Most investigators now believe this to be the major impact of enzyme catalysis

• Anti-entropic Effects: (also called "proximity effects" and "effective concentration"; in solution, reactants must collide to react, a process that has negative entropy (low probability), whereas in the enzyme, all reacting species are essentially intramolecular

• Tunneling can occur in processes involving hydrogen transfer. The implication is that the hydrogen (atom, proton, hydride) can tunnel through the activation barrier rather than surmounting it [Garcia-viloca, Gao, Karplus, Truhlar, Science, 2004, 303, 186]