2. Medical Enzymology By Amr S. Moustafa, M.D.; Ph.D. Assistant Prof. & Consultant, Medical Biochemistry Dept. College of Medicine, KSU amrsm@hotmail.com

3. Michaelis-Menten Equation  E + S ES E + P  v ° = K m : Michaelis constant = (k-1 + k2) / k1 k1 K-1 k2 V max [S] K m + [S]

4. Michaelis-Menten Kinetics

5. Zero and First Order Reactions

6. Lineweaver-Burk Plot = + 1 v°v° KmKm V max [S] 1 V max

7. Inhibition of Enzyme Activity  Inhibitor: The velocity of the reaction  Reversible or irreversible  Competitive or noncompetitive

8. Competitive Inhibition -1  Inhibitors: Structural similarity to S Bind to S-binding site (compete with S) ES or EI complexes [S] overcomes the inhibition  K m But, no effect on V max

9. Competitive Inhibition -2

10.  Statin Drugs, e.g., Simvastatin (Zocor) Competitive Inhibition -3

11. Noncompetitive Inhibition -1  Inhibitors: No structural similarity to S Bind to different (allosteric) site ES or EI or ESI complexes [S] cannot overcome the inhibition  V max But, no effect on K m

12. Noncompetitive Inhibition -2

13. Noncompetitive Inhibition -3

14. Noncompetitive Inhibition -4  Lead and Ferrochelatase  Insecticides and actylcholinesterase  Covalent and irreversible

15. Therapeutic Potential of Enzyme Inhibition  β-Lactam antibiotics, e.g., Penicillin  Angiotensin-converting enzyme (ACE) inhibitors, e.g., Captopril  Statin drugs as antihyperlipidemic