MEDC 527 Fall 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 fold)

MEDC 527 Fall Enzyme Action Three dimensional structure of an enzyme

MEDC 527 Fall Enzyme Action Catalytic Triad Chymotrypsin Acetylcholine Esterase

MEDC 527 Fall Chemical Mechanism of Enzyme Action

MEDC 527 Fall 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?

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

MEDC 527 Fall 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

MEDC 527 Fall [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

MEDC 527 Fall 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

MEDC 527 Fall 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

MEDC 527 Fall 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

MEDC 527 Fall 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 ~ fold

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