2. Topics For Discussion
What are Enzymes
How do Enzymes work
How do we study enzymes
What are Enzyme Inhibitors
How does understanding how an enzyme
works allow the rational design of drugs
3. What Are Enzymes
• Protein
• Catalyst
• Responsible for nearly all of the chemical
reactions that take place in a living cell
4. What is a Catalyst
• Accelerate the rate of a chemical reaction
• Are not consumed by the reaction
5. Rates of Chemical Reaction
• What determines the rate of a chemical
reaction?
6. Reaction Rates
• First… what determines if a reaction goes at
all?
• Must consider the ΔG for the reaction
8. Reaction Direction
• Reactions only proceed spontaneously in
the direction given if the ∆G is negative
• But just because the reaction is
spontaneous, doesn’t mean that it goes at
any measurable rate
9. Transition State Theory
• Consider the conversion of S to P
• -dS/dt = k[S]
• Transition state theory proposes that in the
[S] there is a distribution of energetic forms
and one such form is referred to as the
transition state between S and P.
• The reaction only proceeds through this
form
10.
11. Transition State Theory
• So that the rate of the reaction really is
-dS/dt = k[S*] where S* is the transition
state.
12. [S*]
• So how much [S*] is present
K* = [S*]/[S] where K* is the
equilibrium constant between the transition
state and the ground state
13. Transition State Concentration
• So one can express the [S*] as a function of
the K* and the [S] [S*] = K*[S]
• And since ΔG* = -RTlnK*
• [S*] = e- ΔG*/RT [S]
• And therefore the rate of the reaction would
be -d[S]/dt = ke- ΔG*/RT [S]
• The term in red is the rate constant for the
reaction.
14. • G = free energy at any moment
• G0 = standard-state free energy
• R = ideal gas constant = 8.314 J/mol-K
• T = temperature (Kelvin)
15.
16. Reaction Rate
• Therefore the magnitude of the ∆G*
determines the rate of the reaction
• The lower this value is the faster the
reaction goes
• Therefore, for an enzyme to catalyze a
reaction it must lower the transitions state
free energy (transition state activation
energy)
24. Where Do These General
Acids/General Bases and
Electrostatic Groups Come From
Proteins are linear polymers of amino acids
Some of the Amino Acids have side chains
with functional groups.
28. How Enzymes Catalyze Reactions
• General acid/general base
• Electrostatic
• Change the reaction mechanism
• Proximity and orientation effects
• Entropy considerations
46. Inhibitors
• Why would you want to inhibit an enzyme
• What are the different kinds of enzyme
inhibitors
• How can you know what kind of inhibitor a
molecule is
