The Enzyme Inhibition in medicines.ppt.pptx

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1. Enzyme Inhibitor in Medicine Faculty of Pharmacy, Integral University , Lucknow Presentation on the Topic Presented By- MUSKAN Enrollment No. 2500104535 M. Pharm- Ist year( Ist sem ) Department of Pharmaceutical Chemistry

2. CONTENT Introduction Mechanism of action Classification Inhibition in Medicines Advantages

3. Enzymes are soluble, colloidal, organic catalyst, formed by living cells specific in action, protein in nature, inactive at zero degree celsius and destroyed by moist heat at 100 degree celsius. Emzymes are the specialized protein which catalyze various biochemical reactions. The concept of enzyme inhibition is routinely utilized to affect biosynthesis and metabolic pattern of various hormones, and neurotransmitters. What Are Enzyme ?

4. What are Inhibitors ? Inhibitors are the chemicals that reduces the rate of enzymatic reactions. They are usually specific at work at low concentrations. They block the enzyme but they do not usually destroy it.

5. What Are Enzyme Inhibitors? Enzyme inhibitors are molecules that decrease or block the activity of specific enzymes, thus impacting biochemical reactions crucial for health and disease treatments. They are used both as therapeutic agents (drugs) and in research to regulate or study enzyme function

6. Mechanism and Classification Enzyme inhibitors are molecules that resemble normal substrates or products and bind to the enzyme's active site, interfering with catalysis and slowing or halting enzymatic reactions. The potency of inhibition is defined by how tightly the inhibitor binds, measured using the inhibition constant (Ki)

7. Irreversible Inhibitors Irreversible inhibitors bind covalently to the enzyme or destroy a functional group essential to enzyme activity, leading to permanent inactivation. Example: Diisopropylfluorophosphate (DIFP) binds permanently to Ser195 in chymotrypsin's active site, inhibiting the enzyme and is the basis of organophosphate poisoning treatments

8. Reversible Inhibitors Inhibitor binds to Enzyme reversibly through weak noncovalent interactions. Reversible inhibitors form a non-permanent equilibrium with the enzyme, and their effect depends on concentration and affinity

9. Types of Reversible Enzyme Inhibition

10. The inhibitor competes with substrate and binds at the active site of the enzyme but does not undergo any catalysis. Inhibitor directly competes with the substrate for the enzyme's active site. As long as the competitive inhibitor holds the active site, the enzyme is not available for the substrate to bind. During the reaction, ES and EI complexes are formed. In competitive inhibition, the Km value increases whereas Vmax remains unchanged. Example - methotrexate (used for cancer) and sulfonamides (antibacterial). Competitive Inhibition:

11. Competitive Inhibition Example- Competitive inhibition accounts for the antibacterial action of sulfanilamide which is a structural analog of PABA. Sulfanilamide inhibits the bacterial enzyme dihydropteroate synthetase which catalyzes the incorporation of PABA into 7,8- dihydropteroic acid.

12. Noncompetitive Inhibitor A noncompetitive enzyme inhibitor is a molecule that binds to an enzyme at a site other than the active site (known as the allosteric site), causing a conformational change in the enzyme and reducing its activity Example: A classic example of a noncompetitive enzyme inhibitor is cyanide, which binds to the enzyme cytochrome oxidase and disrupts cellular respiration by inhibiting the electron transport chain.

13. Uncompetitive enzyme inhibition occurs when the inhibitor binds only to the enzyme-substrate complex (not the free enzyme), resulting in a decrease in both the apparent maximum reaction rate (Vmax) and the Michaelis constant (Km), and the inhibition cannot be overcome by increasing substrate concentration Uncompetitive Inhibition

14. Enzyme inhibitors in medicine A selective inhibitor may block either a single enzyme or a group of enzymes. This will result in either a decrease in the concentration of enzymatic products or an increase in the concentration of enzymatic substrates. Low dosage and high specificity combine to reduce the toxicity problems. Enzyme inhibitors used in treatment of bacterial, fungal, viral and parasite diseases The effectiveness of an enzyme inhibitor as a therapeutic agent will depend on: a. The potency of the inhibitor b. Its specificity c. The choice of a metabolic pathway d. The inhibitor or derivative possessing appropriate pharmacokinetic characteristics.

15. Cardiovascular Drugs ACE Inhibitors Target Enzyme: Angiotensin-Converting Enzyme (ACE). Mechanism: Prevents conversion of angiotensin I → angiotensin II (a vasoconstrictor). Examples: Enalapril, Lisinopril, Ramipril. Therapeutic Use: Lowers blood pressure, treats hypertension, heart failure, and diabetic nephropathy. Statins (HMG-CoA Reductase Inhibitors) Target Enzyme: HMG-CoA reductase (rate-limiting enzyme in cholesterol biosynthesis). Mechanism: Blocks conversion of HMG-CoA to mevalonate, lowering cholesterol synthesis. Examples: Atorvastatin, Simvastatin, Rosuvastatin. Therapeutic Use: Reduces LDL cholesterol, prevents atherosclerosis, lowers cardiovascular risk.

16. Target Enzyme: Cyclooxygenase (COX-1 and COX-2, involved in prostaglandin synthesis). Mechanism: Blocks prostaglandin production → reduces pain, fever, and inflammation. Examples: Aspirin, Ibuprofen, Naproxen, Celecoxib (selective COX-2 inhibitor). Therapeutic Use: Analgesic (pain relief), antipyretic (fever reduction), anti-inflammatory. COX Inhibitors (NSAIDs – Non-Steroidal Anti-Inflammatory Drugs)

17. Protease Inhibitors (Antiviral Drugs) Target Enzyme: Viral proteases (essential for viral replication, e.g., HIV, HCV). Mechanism: Prevents cleavage of viral polyproteins → blocks maturation of virus particles. Examples: Ritonavir, Indinavir (HIV); Boceprevir (HCV). Therapeutic Use: Antiretroviral therapy in HIV/AIDS; treatment of Hepatitis C. Reverse Transcriptase Inhibitors (RTIs) Target Enzyme: Viral reverse transcriptase (HIV). Mechanism: Blocks conversion of viral RNA → DNA, preventing viral replication. Examples: Zidovudine (AZT), Lamivudine, Tenofovir. Therapeutic Use: HIV infections

18. Anticancer Drugs Methotrexate (DHFR Inhibitor) Target Enzyme: Dihydrofolate reductase (DHFR). Mechanism: Inhibits folate metabolism → prevents DNA synthesis and cell replication. Examples: Methotrexate. Therapeutic Use: Leukemia, lymphoma, breast cancer, psoriasis, rheumatoid arthritis. 5-Fluorouracil (Thymidylate Synthase Inhibitor) Target Enzyme: Thymidylate synthase. Mechanism: Inhibits thymidylate formation → blocks DNA synthesis in rapidly dividing cells. Examples: 5-Fluorouracil (5-FU), Capecitabine (prodrug). Therapeutic Use: Colorectal cancer, breast cancer, gastrointestinal cancers.

19. ADVANTAGES Precise Disease Control Enzyme inhibitors can selectively block disease-related enzymes, directly targeting the root cause of illness. Example: ACE inhibitors reduce hypertension by blocking angiotensin II formation. High Therapeutic Efficacy Small amounts of inhibitor can cause a large effect because enzymes are catalysts. Allows effective treatment with relatively low doses → fewer side effects. Better Patient Outcomes By blocking harmful biochemical pathways, enzyme inhibitors can reduce symptoms (pain, fever, inflammation), stop disease progression, or even prevent complications.

20. Thank You