Enzyme Inhibition Lecture Notes PDF

Moataz Maher Date: 11-2024  Lecture Objectives 1-Explain the different types of enzyme inhibition. 2-Compare reversible competitive to non competitive enzyme inhibitors and allosteric inhibitors. 3-List some examples of drugs acting as enzyme inhibitors in clinical practice ...

Moataz Maher Date: 11-2024  Lecture Objectives 1-Explain the different types of enzyme inhibition. 2-Compare reversible competitive to non competitive enzyme inhibitors and allosteric inhibitors. 3-List some examples of drugs acting as enzyme inhibitors in clinical practice  Let’s think together  Why do we need enzyme inhibitors?  Enzyme inhibition Enzyme inhibition Reversible Irreversible Competitive Cofacator/coenzyme Non-competitive Denaturation/ppt Allosteric SH group Anti-enzymes  Enzyme Inhibition I- Competitive Inhibitors (Substrate Analogue Inhibitors) 1.Structural similarity between substrate and inhibitor. 2.Both compete for active site 3.Relative conc. 4.Reversed by increase substrate conc.  Enzyme Inhibition I- Competitive Inhibitors (Substrate Analogue Inhibitors) 4.Reversed by increase substrate conc. 5.Km increased 6.Vmax constant 7.The slope is increased  Enzyme Inhibition I- Competitive Inhibitors (Substrate Analogue Inhibitors) 1.Sulfanilamide is bacteriostatic 2.Allopurinol for treatment of gout 3.Dicumarol & Warfarin are anti coagulant  Enzyme Inhibition I- Competitive Inhibitors (Substrate Analogue Inhibitors) 4.Statins competitively inhibit HMG-CoA reductase the key enzyme of cholesterol synthesis. Thus used in the treatment of hypercholesterolemia.  Mention 4 examples of drugs act as competitive inhibitors?  Enzyme inhibition Enzyme inhibition Reversible Irreversible Competitive Cofacator/coenzyme Non-competitive Denaturation/ppt Allosteric SH group Anti-enzymes  Enzyme Inhibition II- Non-Competitive Inhibitors 1.No structural similarity between substrate and inhibitor 2.No competition for active site 3.They bind with site other than the active site 4.Absolute conc. of [I] 5.Not reversed by inc. [S]  Enzyme Inhibition II- Non-Competitive Inhibitors 5.Not reversed by inc. [S] 6.Km is constant 7.Vmax decreased 8.The slope is increased  Enzyme Inhibition II- Non-Competitive Inhibitors Examples: Captopril,  Angiotensin-converting enzyme (ACE) inhibitor  Treatment of hypertension  Compare between Competitive and non competitive inhibition?  Enzyme inhibition Enzyme inhibition Reversible Irreversible Competitive Cofacator/coenzyme Non-competitive Denaturation/ppt Allosteric SH group Anti-enzymes  Enzyme Inhibition III- Allosteric Inhibitors 1.Small organic molecule. 2.Bind with allosteric site 3.Produce conformational change making it Less suitable to bind to substrate (allosteric inhibitor) i.e lead to decrease activity of the enzyme. 4.Km increased &/or 5.Vmax decreased  Enzyme Inhibition III- Allosteric Inhibitors feedback inhibition 1.End product inhibits activity of early enzyme 2.Usually through allosteric inhibition Earliest Irreversible Unique ATP (adenosine triphosphate) is an example of an allosteric inhibitor it inhibits phosphofructokinase a key enzyme in glycolysis.Glycolysis is the process of breaking down glucose to produce ATP in all cells. When the concentration of ATP is too much in the system, then ATP functions as an allosteric inhibitor to prevent excess ATP production. Many antibiotics acts as allosteric inhibitors. Penicillin acts by binding to the bacterial enzyme DD-transpeptidase. The bacteria uses this enzyme to enforce its cell wall and resist lysis.  Summary Reversible Enzyme inhibition. Competitive inhibitors. Non competitive inhibitors. Allosteric inhibitors.