Enzyme Inhibition

• Competitive inhibition is when the inhibitor binds to the active site and prevents the substrate from binding

  • Vmax is unchanged
  • Km is increased
  • Line Weaver burk: slope (Km/Vmax) is increased, y-intercept is unchanged
• Uncompetitive inhibition is when the inhibitor binds to the ES complex and prevents binding

  • Vmax decreases
  • Km decreases
  • Lineweaver burk: inhibition parallel to regular, y-intercept (1/Vmax) increases, slope is unchanged
• Noncompetitive inhibition is when the inhibitor enters another site and deactivates binding

  • Km is unchanged
  • Vmax is decreased
  • Lineweaver burk: slope and y-intercept are increased
• y = mx + b

  1/Vo = Km/Vmax * 1/[S] + 1/Vmax
• Allosteric regulation

  • R state has decreased Km and increased Vmax
  • Hybrid has Increased Km but similar Vmax
  • T state has decreased Km and lesser Vmax
• ATCase produces CTP and has 6 binding sites for ATP

  • when CTP is bound, enzyme enters T state
  • when ATP is bound, enzyme enters R state
• Irreversible inhibition

  • Base - His - uses imidazole to remove H from -OH group of Ser or from -SH of Cys
  • Acid - Glu or Asp - supports His with stabilization throughout process
  • Nucleophile - Ser or Cys - bonds to peptide carbony after removal of H to then allow breaking off of peptide bond
  • H₂O - donates -OH to peptide carbonyl to form carboxylic acid of broken peptide
• Chromotrypsin - hydrolase that uses the catalytic triad in order to lyse C-terminal of Arg/Lys
• α = 1 + [I]/KI
• α' = 1 + [I]/KI'