1. MEDC 527 Fall 20081 Enzyme Action Enzymes … proteins with catalytic function … possess 1 O, 2 O, 3 O and 4 O structure … perform a variety of reactions e.g., hydrolysis, hydroxylation, oxidation, reduction, transfer of groups … … increase the rate of reaction (up to 10 17 -fold)

2. MEDC 527 Fall 20082 Enzyme Action Three dimensional structure of an enzyme

3. MEDC 527 Fall 20083 Enzyme Action Catalytic Triad Chymotrypsin Acetylcholine Esterase

4. MEDC 527 Fall 20084 Chemical Mechanism of Enzyme Action

5. MEDC 527 Fall 20085 Michaelis – Menten Kinetics and Enzyme Inhibition Michaelis-Menten Equation Michaelis-Menten Equation in the presence of a competitive inhibitor What happens at low [S] in the absence of I? What happens at high [S] in the absence of I? What happens at low [S] in the presence of I? What happens at high [S] in the presence of I?

6. MEDC 527 Fall 20086 Reaction Mechanisms Theory of Reaction Rates A + B  C + D

7. MEDC 527 Fall 20087 Reaction Mechanisms Theory of Reaction Rates H 2 C=CH 2 + HCl  H 3 C-CH 2 Cl H 2 C CH 2 H Cl H 3 C CH 2 + Cl - Energy Reaction Co-ordinate Reactants (TS) # Products Transition State EAEA GOGO

8. MEDC 527 Fall 20088 [Conc. Of Reactants] (Z) Temperature (T) Activation Energy (E A ) Probability Factor (P) Reaction Mechanisms Collision Theory Arrhenius Equation … Rate = P × Z × e (–E a /RT) Collision 1 Collision 2 Collision 3 Collision 4

9. MEDC 527 Fall 20089 Reaction Mechanisms Theory of Reaction Rates Arrhenius Equation Rate = P × Z × e (–E a /RT) H pH 5, half–life = 300 yrs pH 5, half–life = 25 days pH 5, half–life = 25 minutes

10. MEDC 527 Fall 200810 Rank the following molecules according to their ability to hydrolyze faster in water at pH 6.0. Use 1 for fastest and 3 for slowest rate of hydrolysis. Reaction Mechanisms Application of Reaction Rate Theory

11. MEDC 527 Fall 200811 Rank the following molecules containing ester/amide group according to their ability to hydrolyze in water at pH 8.0. Use 1 for fastest rate and 3 for slowest rate of hydrolysis. Reaction Mechanisms Application of Reaction Rate Theory

12. MEDC 527 Fall 200812 Reaction Mechanisms Theory of Reaction Rates Energy Reaction Co-ordinate A + B (A…B) # C + D Transition State Activated Complex Transition State in the presence of an enzyme (A..B) # Enzymes! … powerful catalysts 85 yrs 0.01 s _ _ Another example, catalase: 2H 2 O 2  2H 2 O + O 2 E A ~ 18 kcal/mol in absence; ~2 kcal/mol in presence; rate increase of ~10 11 -fold

13. MEDC 527 Fall 200813 Reaction Mechanisms Reaction Rates Consider reactions A) and B). Circle the reaction that has a longer half-life?