1. Chapter 6.3: Enzyme Inhibition CHEM 7784 Biochemistry Professor Bensley

2. CHAPTER 6.3 Enzyme Inhibition –Various types of enzyme inhibition Today’s Objectives: (To learn and understand the)

3. Enzyme Inhibition Inhibitors are compounds that decrease enzyme’s activity Irreversible inhibitors (inactivators) react with the enzyme Reversible inhibitors bind to, and can dissociate from the enzyme Reversible inhibitor can bind: –To the free enzyme and prevent the binding of the substrate –To the enzyme-substrate complex and prevent the reaction

5. Competitive Inhibition Lines intersect at the y-axis

7. Uncompetitive Inhibition Lines are parallel

9. Mixed Inhibition Lines intersect left of the y-axis MAKE SURE YOU DISTINGUISH THIS FROM NON- COMPETITIVE INHIBITION!!!!

10. Viagra (Sildenafil Citrate) Medicinal Inhibitor Example

11. Irreversible Inhibitors Diisopropyl fluorophosphate (nerve gas) parathion malathion Organophosphates Inhibit serine hydrolases Acetylcholinesterase inhibitors

12. Kinetics of Multisubstrate Reactions E + A + B E + P + Q Sequential Reactions (Ternary Complex formed) a) Random b) Ordered Ping-Pong Reactions

13. Sequential Reactions EEA(EAB) (EPQ) EQ E AB P Q AB PQ AB E EA EB (EAB)(EPQ) P Q EQ EP E Ordered Random

14. Ping-Pong Reactions E (EA)(FP) (F) (FB)(EQ) E ABPQ In Ping-Pong rxns first product released before second substrate binds When E binds A, E changes to F When F binds B, F changes back to E

15. Lineweaver-Burke Plot of Multisubstrate Reactions Increasing [B] Increasing [B] Sequential Ping-Pong Vmax doesn’t change Km changes Both Vmax & Km change 1/Vo 1/[S] 1/Vo 1/[S]