Enzyme Inhibition Overview

Enzyme Inhibition Lecture Notes

• The lecture covered enzyme inhibition, specifically focusing on different types of enzyme inhibition, comparisons of various inhibitors, and examples of drugs acting as enzyme inhibitors in clinical practice.

Lecture Objectives

• Explain the different types of enzyme inhibition.
• Compare reversible competitive to non-competitive enzyme inhibitors and allosteric inhibitors.
• List some examples of drugs acting as enzyme inhibitors in clinical practice.

Why Need Enzyme Inhibitors?

• This section discusses the necessity of enzyme inhibitors.

Types of Enzyme Inhibition

• Reversible Inhibitors:

  • Competitive: Structural similarity to the substrate, competes for the active site, reversible by increasing substrate concentration. Increased Km, Vmax constant, increased slope on Lineweaver-Burk plot.
  • Non-competitive: No structural similarity to the substrate, binds to a site other than the active site, absolute concentration of inhibitor, not reversed by increasing substrate concentration. Km constant, decreased Vmax, increased slope on Lineweaver-Burk plot.
  • Allosteric: Small organic molecules bind to an allosteric site, changing enzyme conformation, affecting substrate binding, Km increased or Vmax decreased.

• Irreversible Inhibitors:

  • Cofactor/coenzyme: Inhibitor interferes with cofactor/coenzyme binding.
  • Denaturation/ppt: Inhibitor causes enzyme denaturation.
  • SH group: Inhibitor reacts with SH group of the enzyme.
  • Anti-enzymes: Inhibitor is a protein that inhibits specific enzymes.

Competitive Inhibitors (Substrate Analogue Inhibitors)

• Structural similarity between substrate and inhibitor.
• Both compete for the active site.
• Relative concentration of substrate and inhibitor.
• Reversed by increasing substrate concentration.
• Km increased, Vmax constant.
• The slope is increased on Lineweaver-Burk plot

Examples of Competitive Inhibitors

• Sulfanilamide: Bacteriostatic, a PABA analogue.
• Allopurinol: Used in gout treatment.
• Dicumarol & Warfarin: Anti-coagulants.
• Statins: Competitive inhibitors of HMG-CoA reductase, used in hypercholesterolemia treatment.

Non-Competitive Inhibitors

• No structural similarity between substrate and inhibitor.
• No competition for the active site.
• Bind to a site other than the active site.
• Absolute concentration of inhibitor.
• Not reversed by increasing substrate concentration.
• Km constant, Vmax decreased.
• The slope is increased on Lineweaver-Burk plot.

Examples of Non-Competitive Inhibitors

• Captopril: Angiotensin-converting enzyme (ACE) inhibitor used in hypertension treatment.

Allosteric Inhibitors

• Small organic molecules.
• Bind to the allosteric site.
• Produce conformational change, making binding to substrate less suitable (decrease enzyme activity).
• Km increased or/and Vmax decreased.

Allosteric Feedback Inhibition

• End product inhibits the activity of an early enzyme within a pathway.
• Usually irreversible.
• Important in metabolic regulation.
• ATP is an example (inhibits phosphofructokinase, a key enzyme in glycolysis).

Summary

• Reversible enzyme inhibition.
• Competitive inhibitors.
• Non-competitive inhibitors.
• Allosteric inhibitors.

This quiz covers key concepts of enzyme inhibition, focusing on various types such as reversible competitive and non-competitive inhibitors. It also discusses their clinical applications and the importance of enzyme inhibitors in medicinal chemistry. Test your understanding with questions based on these crucial topics!