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Transcript
Enzymes and the Arrhenius Equation
Enzymes
Catalysts for Biochemical Reactions
ƒEnzymes bring reactants together in the proper
orientation for reaction to occur.
ƒEnzymes speed up the reaction by stabilizing the
transition state.
ƒReaction proceeds via a different mechanism in
the presence of the enzyme.
k=Ae-Ea/RT
Enzymes lower the activation
energy by allowing the reaction to
proceed via a different mechanism.
Enzymes increase the fraction of
productive collisions by binding
the reacants in the proper
orientation for reaction to occur.
A = pZ
Enzymes
How Do Enzymes Work?
Reaction Mechanisms
By Stabilizing the Transition State
The enzyme surrounds the forming
transition state with favorable
interactions. Stabilization of this
transition state by binding to the
enzyme results in a lower activation
energy, and thus a faster rate of
reaction for the enzyme-catalyzed
reaction.
Uncatalyzed Reaction
S
P
Energy
Energy
ES
ES
Catalyzed Reaction
E + S
ES
ES
P + E
S
P
S
P
Reaction Progress
Key:
S = substrate
E = enzyme
ES = enzyme-substrate complex
P = product
Reaction Progress
Enzyme-catalyzed reaction
Uncatalyzed reaction
Substrate Binding
Enzyme Activity
The Active Site
Enzymes bind the substrate (reactants) in the active site. This is a
cleft that is lined with an array of polar, non-polar, and charged
amino acids arranged in such a way as to interact favorably, and
selectively, with the substrate.
The Native Structure
Acetylcholinesterase
HIV Protease
Enzymes fold into a specific shape called the native structure. If the enzyme
is unfolded from this structure (denatured), it no longer functions as a
catalyst. The native structure is held together largely by a combination of
non-covalent interactions (H-bonding, charge-charge, dispersion, etc.). If the
pH or temperature conditions change from the optimal ones, these
interactions are disturbed and the enzyme will denature and no longer act as a
catalyst.
1
Case Study
Acetylcholine
Acetylcholinesterase
A Neurotransmitter
•Essential for nerve transmission at neuromuscular
junctions (nerve-muscle connections)
•Removes excess acetylcholine (neurotransmitter)
from synapse allowing neuron to reload and fire
next nerve impulse.
•Target of nerve agents (Sarin, Tabun, Soman, etc)
:O:
CH3
H3C
+
N
..
CH2 CH2 O
..
CH3
C
CH3
Ester Group
Ammonium Group
Acetylcholine is a neurotransmitter; a chemical
messenger that propagates the nerve impulse across
a synapse (gap between neurons).
Nerve Transmission
Nerve Transmission
Receptors
Resting State
Acetylcholinesterase (AChE) clears
the excess ACh out of the synapse by
hydolytic cleavage. When the synaptic
ACh concentration is reduced,
acetylcholine diffuses away from the
receptors (Le Chatelier's principle).
Acetylcholine (ACh) diffuses across
the synapse. When ACh binds to
receptors on the other side of the
synapse, it triggers changes in ion
concentration that result in an
electrical impulse. This signal is
passed on to the next nerve and the
process repeats itself down the line.
= Acetylcholine (ACh)
Acetylcholinesterase plays a major
role in the nerve transmission process.
The excess ACh present in the synapse
must be removed so that the nerve cell
is ready for the next nerve impulse.
= Acetylcholinesterase (AChE)
Reaction Catalyzed by
Acetylcholinesterase
Acetylcholinesterase
Reverse of Condensation Reaction
Catalytic Triad
CH 3
H3C
N
+
CH 3
Histidine 440
O
CH 2 CH 2 O
C
CH 3 +
H 2O
Acetylcholine
N
+
CH 3
Serine 200
O
CH 3
H3C
CH2 CH 2 O H + H O
C
Inhibitor
CH 3
Glutamate 199
These three amino acids, the catalytic triad,
are located at the active site and play a crucial
role in catalysis.
2
Nerve Agents
Nerve Agents
Nerve agents work by reacting with the OH group
of the active-site serine that is required for catalytic
activity. This disables (inhibits) the enzyme.
Sarin
O
F
P CH3
F
P CH3
CH3CH2
O P CH3
S
HC CH3
H3C CH CH3
H3C C CH3
CH3
CH2
H3C CH N CH CH3
CH3
Sarin
O
CH2
HO
..:
O
O
O
Active
Site
ser
VX
Soman
O
Inhibition of Acetylcholinesterase
F
P CH3
O
O
ser
CH2 O
P CH3
+ HF
O
CH CH3
CH CH3
CH3
CH3
Inactivated Enzyme
CH3
Exercises
1. Draw the Lewis structure of the dipeptide Val-Ser. (Hint: The structures of these amino acids
appear on the “Examples of Amino Acids” slide in this presentation.)
2. The amino acid valine has a hydrocarbon sidechain. In the native (folded) structure of a
water-soluble protein, would you expect to find the majority of the valines on the exterior of the
protein or in the interior. Explain your answer.
3. Which terms of the Arrhenius Equation are favorably affected by the action of enzymes?
4. A chemist measures the rate of an enzyme-catalyzed reaction as a function of temperature and
obtains a relationship such as that shown in the plot below. Provide an explanation. Is this the
relationship between rate and temperature that is found for reactions that do not involve
enzymes?
Rate
Temperature
3