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MEDC 527 Fall 2008 1
Enzyme Action
Enzymes … proteins with catalytic function
… possess 1O, 2O, 3O and 4O structure
… perform a variety of reactions e.g., hydrolysis, hydroxylation,
oxidation, reduction, transfer of groups …
… increase the rate of reaction (up to 1017-fold)
MEDC 527 Fall 2008 2
Enzyme Action
Three dimensional structure of an enzyme
MEDC 527 Fall 2008 3
Enzyme Action
Catalytic Triad Catalytic Triad Chymotrypsin Acetylcholine Esterase
MEDC 527 Fall 2008 4
Chemical Mechanism of Enzyme Action
MEDC 527 Fall 2008 5
Michaelis – Menten Kinetics and Enzyme Inhibition
][
][
SK
SVVi
M
MAX
][}][
1{
][
SK
IK
SVVi
IM
MAX
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 2008 6
Reaction Mechanisms
Theory of Reaction Rates
A + B C + D
MEDC 527 Fall 2008 7
Reaction Mechanisms
Theory of Reaction Rates
H2C=CH2 + HCl H3C-CH2Cl
H2C CH2
H
Cl
H3C CH2
+
Cl-
En
erg
yReaction Co-ordinate
Reactants
(TS)#
Products
Transition State
EA
GO
MEDC 527 Fall 2008 8
• [Conc. Of Reactants] (Z)• Temperature (T)• Activation Energy (EA)• Probability Factor (P)
Reaction Mechanisms
Collision Theory• Arrhenius Equation … Rate = P×Z×e(–Ea/RT)
Collision 1 Collision 2
Collision 3 Collision 4
MEDC 527 Fall 2008 9
Reaction Mechanisms
Theory of Reaction Rates• Arrhenius Equation Rate = P×Z×e(–Ea/RT)
NH
CH3
O
NH
CH
2
OHOOC
N
O
OH
OMe
MeMe
MeH
pH 5, half–life = 300 yrs
pH 5, half–life = 25 days
pH 5, half–life = 25 minutes
MEDC 527 Fall 2008 10
NH
OCH3
NH
OCH3C3H7
NH
OCH3
HOOC
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 2008 11
CH3
CH3
OO CH3
COOHCH3
OO CH3
Cl CH3
OO CH3
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 2008 12
Reaction Mechanisms
Theory of Reaction Rates
En
erg
y
Reaction Co-ordinate
A + B
(A…B)#
C + D
Transition StateActivated Complex
Transition Statein the presenceof an enzyme
(A..B)#
• Enzymes! … powerful catalysts
CH3
O
OEt CH3
O
O
CH
O
OEt
NOH H Ac
CH
O
O
NOH H Ac
85 yrs
0.01 s _
_
Another example, catalase: 2H2O2 2H2O + O2
EA ~ 18 kcal/mol in absence; ~2 kcal/mol in presence; rate increase of ~1011 -fold
MEDC 527 Fall 2008 13
Reaction Mechanisms
Reaction Rates
OCH2CH3
O
OH
OHO
CH3
CH3
CH3
CH3
OCH2CH3
O
t1/2
H2O/OH-, pH 12.0
t1/2
A)
B)
H2O/OH-, pH 12.0
Consider reactions A) and B). Circle the reaction that has a longer half-life?
