Drug Action by Enzyme Inhibition

Enzyme inhibition is a key mechanism by which drugs exert their effects. It involves the interference with the activity of enzymes, which are proteins that catalyze biochemical reactions in the body. Here’s a breakdown of how this works:

Types of Enzyme Inhibition

1. Competitive Inhibition:

   • Mechanism: The inhibitor resembles the substrate and competes for the active site of the enzyme.
   • Effect: Increases the apparent Km (Michaelis constant) of the enzyme, meaning that a higher concentration of substrate is needed to achieve half-maximal velocity (Vmax). However, Vmax remains unchanged.

2. Non-competitive Inhibition:

   • Mechanism: The inhibitor binds to an allosteric site (a site other than the active site) on the enzyme, altering its shape and function.
   • Effect: Vmax decreases because the enzyme's ability to catalyze the reaction is reduced, but Km remains the same since the substrate can still bind.

3. Uncompetitive Inhibition:

   • Mechanism: The inhibitor binds only to the enzyme-substrate complex, preventing the complex from releasing products.
   • Effect: Both Vmax and Km decrease, as the inhibitor stabilizes the enzyme-substrate complex, making it less likely to proceed to the product.

4. Irreversible Inhibition:

   • Mechanism: The inhibitor forms a covalent bond with the enzyme, permanently disabling it.
   • Effect: This leads to a permanent loss of enzyme activity, often requiring the synthesis of new enzyme molecules for function to resume.

Examples in Pharmacology

• Competitive Inhibitors: Statins inhibit HMG-CoA reductase, an enzyme involved in cholesterol synthesis, thereby reducing cholesterol levels.
• Non-competitive Inhibitors: Lithium can inhibit inositol monophosphatase, affecting signaling pathways in bipolar disorder.
• Irreversible Inhibitors: Aspirin irreversibly inhibits cyclooxygenase (COX) enzymes, reducing inflammation and pain.

Importance

Understanding enzyme inhibition is crucial for drug design and development, as it allows for the creation of medications that can specifically target and modulate metabolic pathways, improving therapeutic outcomes while minimizing side effects.