1.12 Clinical applications of enzyme inhibition

Summary

This lecture by Dr. Chandra Kenai explores the clinical applications of enzyme inhibition in medicine. It begins with the basics of enzymes and their role as biological catalysts, then explains enzyme inhibitors, focusing on competitive inhibition, where inhibitors resemble substrates and temporarily block enzyme activity. The session highlights how understanding competitive inhibition enables drug design to treat various conditions, including bacterial infections, cancer, hypercholesterolemia, gout, hypertension, and viral infections. Key examples of drugs and their target enzymes, such as statins, methotrexate, allopurinol, and NSAIDs, illustrate the therapeutic relevance, emphasizing the importance of enzyme-substrate mimicry in modern pharmacology.

Takeaways

• 😀 Enzymes are catalysts that speed up biochemical reactions, converting substrates to products.
• 😀 Enzymes are primarily proteins, and sometimes RNA molecules, that help regulate metabolic pathways in the body.
• 😀 Enzyme inhibitors can either temporarily or permanently reduce enzyme activity, with reversible inhibitors being the most common.
• 😀 Competitive enzyme inhibition occurs when the inhibitor resembles the enzyme's substrate, competing for the active site.
• 😀 Competitive inhibition is reversible, meaning adding more substrate can overcome the inhibitor's effect.
• 😀 In clinical medicine, competitive inhibitors are used in drug design to block specific enzymes involved in disease processes.
• 😀 Examples of drugs based on competitive enzyme inhibition include statins (for cholesterol), methotrexate (anti-cancer), and sulfa drugs (antibacterial).
• 😀 Competitive enzyme inhibitors can be used to treat metabolic diseases, prevent the accumulation of unwanted metabolites, and treat infections.
• 😀 Competitive inhibition can be applied to specific pathways, such as blocking cholesterol production or inhibiting bacterial growth.
• 😀 Knowledge of enzyme inhibition has led to the development of various drugs, such as allopurinol (for gout), methotrexate (for cancer), and statins (for hypercholesterolemia).

Q & A

What is the primary function of enzymes in biochemical reactions?

Enzymes act as catalysts, speeding up biochemical reactions by converting substrates into products without being consumed in the process.

What is the difference between reversible and irreversible enzyme inhibition?

Reversible enzyme inhibition is temporary, where the inhibitor can dissociate from the enzyme. Irreversible inhibition results in permanent enzyme inactivation, often through covalent bonding with the enzyme.

How do competitive inhibitors affect enzyme activity?

Competitive inhibitors resemble the enzyme's substrate and compete for the active site, which can be overcome by increasing the concentration of the substrate.

Can competitive inhibition be reversed?

Yes, competitive inhibition is reversible. The inhibition can be reduced or overcome by increasing the concentration of the substrate.

What are the therapeutic uses of competitive enzyme inhibitors?

Competitive enzyme inhibitors are used in treating bacterial infections, viral infections, cancers, hypercholesterolemia, and metabolic disorders like gout and hypertension.

What is the mechanism of action of statins in treating hypercholesterolemia?

Statins, such as simvastatin, inhibit the enzyme HMG-CoA reductase, which is responsible for cholesterol synthesis in the liver, thereby reducing blood cholesterol levels.

What is 5-fluorouracil used for in medical treatments?

5-fluorouracil is an anti-cancer agent used in chemotherapy to inhibit the synthesis of DNA and RNA, thereby preventing cancer cell proliferation.

How does methotrexate function as an anti-cancer drug?

Methotrexate is an antimetabolite that inhibits the enzyme dihydrofolate reductase, blocking the synthesis of tetrahydrofolate, which is necessary for DNA synthesis and cell division.

What enzyme does allopurinol inhibit and for what condition?

Allopurinol inhibits the enzyme xanthine oxidase, which reduces the production of uric acid and is used in treating gout.

How do proton pump inhibitors like omeprazole work?

Proton pump inhibitors, like omeprazole, inhibit the H+/K+ ATPase pump in the stomach lining, reducing gastric acid production and providing relief from conditions like acid reflux.