Enzyme Inhibition Lecture

Enzyme Inhibition - Lecture Notes

• Lecture Objectives:
  • Explain different types of enzyme inhibition.
  • Compare reversible competitive and non-competitive enzyme inhibitors, and allosteric inhibitors.
  • List examples of drugs acting as enzyme inhibitors in clinical practice.

Types of Enzyme Inhibition

• Reversible Inhibition:

  • Competitive Inhibition:
    • Structural similarity between substrate and inhibitor.
    • Both compete for the active site.
    • Relative concentration affects inhibition.
    • Increased substrate concentration reverses inhibition.
    • Km increases, Vmax remains constant.
    • Slope of Lineweaver-Burk plot increases.
    • Example: Sulfanilamide (bacteriostatic), statins (inhibit HMG-CoA reductase, used for hypercholesterolemia),
  • Non-competitive Inhibition:
    • No structural similarity between substrate and inhibitor.
    • No competition for active site.
    • Inhibitor binds to a site other than the active site, altering the enzyme's shape.
    • Absolute inhibitor concentration affects inhibition..
    • Not reversed by increased substrate concentration.
    • Km remains constant, Vmax decreases.
    • Slope of Lineweaver-Burk plot increases.
    • Example: Captopril (ACE inhibitor, used for hypertension).
  • Allosteric Inhibition:
    • Small organic molecules bind to an allosteric site on the enzyme.
    • This causes a conformational change, making it less suitable for binding to the substrate.
    • Decreases enzyme activity.
    • Km increases, Vmax decreases.
    • Example: ATP (inhibits phosphofructokinase).

• Irreversible Inhibition:

  • Cofactor/coenzyme disruption.
  • Denaturation/precipitation.
  • SH group modification.
  • Anti-enzyme formation.

Competitive Inhibitors (Substrate Analogues)

• Mechanism of action:
  • Competitive inhibitors have a structure similar to the substrate.
  • They compete with the substrate for binding to the active site.
  • When the inhibitor binds, the enzyme can't bind to the substrate and no product is made.
  • The amount of inhibition depends on the relative concentrations of substrate and inhibitor

Non-competitive Inhibitors

• Mechanism of action:
  • Non-competitive inhibitors bind to a site other than the active site and alter the enzyme's shape.
  • This changes the active site, preventing the substrate from binding effectively.
  • The inhibition is not reversible by increasing substrate concentration.

Allosteric Inhibitors

• Mechanism of action:
  • These inhibitors bind an allosteric site.
  • The binding induces a conformational change altering the active site.
  • This impacts the enzyme's ability to bind its substrate (and hence catalyze a reaction).

This quiz explores the various types of enzyme inhibition, including reversible competitive and non-competitive inhibition, as well as allosteric inhibitors. You'll also learn about the impact of these inhibitors on enzyme kinetics and their relevance in clinical practice. Test your understanding of key examples and concepts in enzyme inhibition.