Mechanism of Drug action by Enzyme Stimulation and Inhibition

 The mechanism of drug action through enzyme stimulation and inhibition involves modulating the activity of enzymes, which are biological catalysts essential for various physiological processes. Here’s how these two mechanisms work:

1. Enzyme Stimulation (Activation)

Drugs that stimulate enzymes increase their catalytic activity, enhancing the rate of biochemical reactions. This can be achieved by:

• Allosteric Activation: Some drugs bind to an allosteric site (a site on the enzyme other than the active site), which changes the enzyme's conformation, increasing its activity. This makes the enzyme more effective at converting substrates into products.
• Proenzyme Activation: Some drugs can promote the conversion of inactive proenzymes (zymogens) into their active forms, thereby boosting enzymatic activity. For example, digestive enzymes are often secreted as inactive precursors and activated only when needed.

Example:

• Nitroglycerin: In cardiovascular therapy, nitroglycerin stimulates the enzyme guanylate cyclase, leading to the production of cyclic GMP, which causes blood vessel relaxation.

2. Enzyme Inhibition

Drugs that inhibit enzymes reduce or block their activity, slowing down or halting specific biochemical reactions. This can occur in several ways:

• Competitive Inhibition: The drug competes with the substrate for binding to the enzyme's active site. Since both cannot bind simultaneously, the enzyme's activity is reduced. The inhibition can be reversed by increasing the concentration of the substrate.

  Example:

  • Methotrexate inhibits dihydrofolate reductase, which is essential for DNA synthesis, and is used in cancer chemotherapy.

• Non-Competitive Inhibition: The drug binds to a site other than the active site (allosteric site), causing a conformational change in the enzyme that decreases its activity. This type of inhibition cannot be overcome by increasing the substrate concentration.

  Example:

  • Cyanide is a potent inhibitor of cytochrome c oxidase, an enzyme involved in the electron transport chain in mitochondria, leading to cellular respiration failure.

• Irreversible Inhibition: The drug forms a covalent bond with the enzyme, permanently deactivating it. The enzyme can no longer function even if the drug is removed, and new enzyme molecules must be synthesized to restore activity.

  Example:

  • Aspirin irreversibly inhibits cyclooxygenase (COX) enzymes, reducing the production of prostaglandins, which are involved in inflammation and pain signaling.

Summary:

• Enzyme stimulation increases enzyme activity, enhancing physiological processes.
• Enzyme inhibition decreases or halts enzyme activity, preventing certain reactions from taking place. Both mechanisms are critical in designing drugs that regulate metabolic pathways or target specific diseases.