1. SURVEY OF BIOCHEMISTRY Enzyme Kinetics and Inhibition

2. Rates of Chemical Reactions
Enzyme kinetics is the study of rates of reactions catalyzed by enyzmes.
v = A P k
The rxn rate (velocity, v) can be described in several ways:
[1] disappearance of reactant, A
[2] appearance of product, P
These eqn’s relate velocity to concentration of reactants and products.

3. Rate Laws
Enzyme kinetics is the study of rates of reactions catalyzed by enyzmes.
v = A P k
A rate law is an equation describing the velocity of a chemical reaction.
Differential Rate Laws
Integrated Rate Laws

4. Differential Rate Laws
Differential rate laws correspond to order of the reaction.
Order of Reaction Rate Law
0 v = k
1 v = k [A]
2 v = k [A]2 or k[B]2 or
v = k [A] x [B]

5. Integrated Rate Laws: First Order
Integrated rate laws express the rxn velocity in terms of time.
A products
Rate of Disappearance of A
- d[A] dt
= k [A] first order rxn
Rearranging…
d[A]
[A]
= - k dt

6. Integrated Rate Laws: First Order
Rearranging…
d[A]
[A]
= - k dt
[A]t
Integrate on both sides of eqn: dA =
- k dt
[A]0
(ln [A]t + constant) - (ln [A]0 + constant) = - kt
ln [A]t - ln [A]0 = - kt

7. Integrated Rate Laws: First Order
ln [A]t - ln [A]0 = - kt
ln [A] = ln [A]0 - kt

8. Integrated Rate Law: Other Versions of First Order
ln [A]t - ln [A]0 = - kt ln
[A]t
[A]0
= - kt
first order rxn
Rearranging:
Take exponent of both sides:
[A]t
[A]0
= e -kt
[A]t = [A]0 e -kt
first order rxn

9. Integrated Rate Law: Second Order
How does the integrated rate law change if the order of the reaction is second order?
2A products
Rate of Disappearance of A
- d[A] dt
= k [A]2 second order rxn
Show result on board
Rearranging…
d[A]
[A]2
= - k dt

10. Michaelis-Menten Equation
Many enzymes obey Michaelis-Menten kinetics behavior:
E + S ES E + P k1
k-1 k2
Rate limiting step
Problem:
[ES] is difficult to measure! What can we do?

11. Michaelis-Menten Equation
E + S ES E + P k1
k-1 k2
Recall
Assume equilibrium is maintained in 1st step
Assume “steady state”
k1 [E] [S] - k-1 [ES] - k2 [ES] = 0
Formation of ES
Depletion of ES
See notes on board…

12. Michaelis-Menten Kinetics

13. Lineweaver-Burk Plot

14. bind to different site in E than S
Enzyme Inhibition
What is an inhibitor?
Modes of Inhibition
Competitive binds to same site in E as S
Uncompetitive
Noncompetitive
Mixed
bind to different site in E than S
Note: Text does not distinguish “non” and “mixed”

15. Competitive Inhibition
Competitive inhibitors bind to the same site on E as S

16. Competitive Inhibition

17. Competitive Inhibition

18. Uncompetitive Inhibition
Uncompetitive inhibitors bind directly to the ES complex but not to the free enzyme

19. Uncompetitive Inhibition

20. Mixed Inhibition
Mixed inhibitors can bind to E or ES complex S cannot bind if I is already bound!

21. Mixed Inhibition

22. Noncompetitive Inhibition
Noncompetitive inhibitors can bind to E or ES complex S can bind even if I is already bound!
+ I
See board for plot

23. Exam #2 in two weeks (June 26)
Updates and Reminders
Exam #2 in two weeks (June 26)
Chapter 7: Protein Function
Chapter 11: Enzyme Catalysis
Chapter 12: Kinetics & Inhibition
Chapter 8: Carbohydrates
Chapter 14: Introduction to Metabolism
Suggested HW problems online this weekend
Resources: What You Should Know more coming soon