1. Mechanisms of Enzyme Action

2. Kinetics of an uncatalyzed chemical reaction:
S S* P
Free energy, G
“Reaction coordinate”
Ea is “activation energy”

3. Kinetics of a catalyzed chemical reaction:
S + E ES ES* EP E + P
Free energy, G
“Reaction coordinate”
Enzyme does not affect G or Go between S and P (i.e., equilibrium)
Enzyme reduces Ea: Ea (catalyzed) < Ea (uncatalyzed)

4. A more complete way of showing the effects of enzymes:
Enzymes bind to
substrates, so
G(ES) < G(E+S).
However, if all they
did was to bind, then Ea
G(ES*) for the reaction
would not be reduced.
So when they bind the
substrate, they stress
It in some way, raising
G(ES) for part of the
substrate and reducing
G(ES*)(=Ea).

5. Quantitatively, what is the effect of reducing Ea?

6. How do enzymes reduce Ea?

10. Asp-His-Ser = DHS

11. e- movement
Low-barrier hydrogen bond:
e- movement

12. (same picture as previous)

13. Cleavage of the
peptide bond
Release of the
amino product

14. (same picture as previous)

15. e- movement
e- movement
ser-substrate bond breaks

16. (same picture as previous)

17. DHS regenerated

19. Summary
Enzymes speed reactions by reducing Ea
Enzyme reduce Ea by stressing substrate (raising G(ES))
and by reducing G(ES*)
Lysozyme and chymotrypsin give examples of enzyme pathways for hydrolysis