Enzyme Inhibitors Lecture

Non-Competitive Inhibitors

• Definition: Non-competitive inhibitors are molecules that bind to an enzyme at a location other than the active site, known as the allosteric site.

  • Do not compete with substrates for the active site.
  • Binding changes the enzyme's 3D structure, preventing substrate binding and thus no enzyme-substrate (ES) complex formation.
  • Inhibition is reversible; upon detachment, the enzyme's shape and function can return to normal.

• Effects on Enzyme Activity:

  • Disrupts hydrogen bonds and hydrophobic interactions, altering enzyme shape.
  • Results in decreased enzyme activity as the substrate cannot bind to the active site.
  • Increasing substrate concentration does not affect non-competitive inhibitors’ ability to inhibit the enzyme.

• Impact on Vmax:

  • Non-competitive inhibitors lower the Vmax (maximum rate of reaction) as they decrease the number of active enzymes available.
  • Unlike competitive inhibitors, Vmax cannot be reached by increasing substrate concentration.

Experiment Insights

• Without Inhibitors:

  • Reaction rate increases proportionally with substrate concentration until Vmax is reached, due to limited enzyme concentration.

• With Non-Competitive Inhibitors:

  • Initial reaction rate increases with substrate concentration but cannot reach original Vmax.
  • Shows that excess substrates cannot overcome non-competitive inhibition.

Natural Occurrence and Benefits

• Non-competitive inhibition occurs naturally in the body to regulate metabolic pathways and prevent the overproduction of end products.

  • Chain reactions involve multiple enzymes to convert initial substrates to end products.

• End Product Inhibition:

  • End products can bind to the allosteric site of the first enzyme in a pathway, inhibiting further production.
  • Prevents excess end product accumulation which could be harmful.
  • Conserves substrates for future use.

• Example:

  • Conversion of threonine to isoleucine is regulated to avoid depleting threonine, which is essential for protein synthesis.
  • Isoleucine acts as a non-competitive inhibitor to maintain balance between the two amino acids.

Key Points for Exams

• Understand that non-competitive inhibitors bind to sites other than active sites.
• Inhibition is reversible and not overcome by increased substrate concentration.
• Recognize the role of non-competitive inhibitors in natural regulatory mechanisms like end product inhibition.