Enzymes

Substrate Specificity of Enzymes

  • Enzyme’s substrate: the reactant that an enzyme acts on
  • The enzyme binds to its substrate, forming an enzyme-substrate complex
  • Active site: the region on the enzyme where the substrate binds
  • Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction

Catalyst’s in the Enzyme’s Active Site

  • In an enzymatic reaction, the substrate binds to the active site of the enzyme
  • The active site can lower an EA barrier by
    • Orienting substrates correctly
    • Straining substrate bonds
    • Providing a favorable microenvironment
    • Covalently bonding to the substrate

Mechanisms

  • Proximity and Strain Effects
    • Substrate fits the catalytic site with proper orientation to catalytic groups. 
    • Enzyme conformation changes to give a strained E-S complex.  
    • Facilitates attaining the transition state. 
  • Electrostatic Effects
    • Substrate binding site excludes H2O & lowers the dielectric constant strengthening electrostatic interaction between E and S.
  • Acid-Base Catalysis
    • Enzyme side chains act as proton donors and acceptors.
  • Covalent Catalysis
    • Powerful nucleophilic side chain forms an unstable covalent bond to the substrate.

Enzyme Specificity

  • Typically a pocket or groove on the surface of the protein into which the substrate fits.
  •  The specificity of an enzyme – fit between the active site and that of the substrate
    • Specificity is controlled by the structure - the unique fit of substrate with enzyme controls the selectivity for substrate and the product yield
  • Enzyme changes shape– tighter induced fit, bringing chemical groups in position to catalyze the reaction.
  • Enzymes are highly specific for the kind of reaction they catalyze, but is not always true of substrates they attack
    • Succinic dehydrogenase always catalyzes an oxidation-reduction reaction and its substrate is invariably succinic acid
    • Alcohol dehydrogenase always catalyzes oxidation-reduction reactions but attacks a number of different alcohols.
  • Enzymes also are generally specific for a particular steric configuration (optical isomer) of a substrate

Additional Requirements for Enzymes

  • Prosthetic groups: small molecules permanently attached to the enzyme
  • Cofactor: usually inorganic ion that temporarily binds to enzyme
  • Coenzyme: organic molecule that participates in reaction but is left unchanged afterward