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Chapter 6.3: Enzyme Inhibition

Chapter 6.3: Enzyme Inhibition. CHEM 7784 Biochemistry Professor Bensley. CHAPTER 6.3 Enzyme Inhibition. Various types of enzyme inhibition. Today’s Objectives : (To learn and understand the). Enzyme Inhibition. Inhibitors are compounds that decrease enzyme’s activity

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Chapter 6.3: Enzyme Inhibition

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

  2. CHAPTER 6.3Enzyme 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

  4. Competitive Inhibition Lines intersect at the y-axis

  5. Uncompetitive Inhibition Lines are parallel

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

  7. Medicinal Inhibitor Example Viagra (Sildenafil Citrate)

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

  9. Kinetics of Multisubstrate Reactions E + A + B <-> E + P + Q • Sequential Reactions (Ternary Complex formed) • Random • Ordered • Ping-Pong Reactions

  10. Q P A B E EA (EAB) (EPQ) EQ E P Q A B EA EQ (EAB)(EPQ) E E EB EP Sequential Reactions Ordered Random Q P B A

  11. A P B Q E (EA)(FP) (F) (FB)(EQ) E Ping-Pong Reactions • 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

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

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