ch06 Enzymes
ch06 Enzymes
ch06 Enzymes
-
• Metabolites have many
-
O COO
potential pathways of
OH COO
decomposition
-
O COO -
- Chorismate
OH - COO
COO mutase
OOC • Enzymes make the
O
desired one most
favorable
NH2 OH
Enzymatic Substrate Selectivity
OH
H
H
- +
OOC NH3 - +
OOC NH3
H
-
OOC
+
NH3
No binding
OH
HO OH
H
H
H Binding but no reaction
NH
CH3
37˚C
pH ≈7
Six Classes of Enzymes:
Defined by the Reactions Catalyzed
Enzyme-Substrate Complex
• Enzymes act by binding substrates
– The noncovalent enzyme substrate complex is
known as the Michaelis complex
– Description of chemical interactions
– Development of kinetic equations
kcat [ E ][ S ]
v
K m [S ]
Enzyme-Substrate Complex
Enzymatic Catalysis
• Enzymes do not affect equilibrium (ΔG)
• Slow reactions face significant activation
barriers (ΔG‡) that must be surmounted
during the reaction
• Enzymes increase reaction rates (k) by
decreasing ΔG‡
kB T G
k exp
h RT
Reaction Coordinate Diagram
Enzymes Decrease ΔG‡
Rate Enhancement by Enzymes
How to Lower G
Enzymes organize reactive groups into close
proximity and proper orientation
• Uncatalyzed bimolecular reactions
two free reactants single restricted transition state
conversion is entropically unfavorable
• Uncatalyzed unimolecular reactions
flexible reactant rigid transition state conversion is
entropically unfavorable for flexible reactants
• Catalyzed reactions
Enzyme uses the binding energy of substrates to organize
the reactants to a fairly rigid ES complex
Entropy cost is paid during binding
Rigid reactant complex transition state conversion is entropically OK
Support for the Proximity Model
The rate of anhydride formation from esters and carboxylates
shows a strong dependence on proximity of two reactive groups
(work by Thomas C. Bruice’s group).
How to Lower G
Enzymes bind transition states best
• The idea was proposed by Linus Pauling in 1946
– Enzyme active sites are complimentary to the
transition state of the reaction
– Enzymes bind transition states better than substrates
– Stronger/additional interactions with the transition
state as compared to the ground state lower the
activation barrier