Enzymes Enzymes and the Arrhenius Equation

Catalysts for Biochemical Reactions

ƒEnzymes bring reactants together in the proper

Enzymes lower the activation
orientation for reaction to occur. k=Ae-Ea/RT energy by allowing the reaction to
ƒEnzymes speed up the reaction by stabilizing the proceed via a different mechanism.

transition state.
ƒReaction proceeds via a different mechanism in
Enzymes increase the fraction of
the presence of the enzyme. productive collisions by binding A = pZ
the reacants in the proper
orientation for reaction to occur.

Enzymes How Do Enzymes Work?

Reaction Mechanisms By Stabilizing the Transition State
The enzyme surrounds the forming
Uncatalyzed Reaction transition state with favorable
interactions. Stabilization of this
S P Energy
transition state by binding to the
enzyme results in a lower activation
ES Energy energy, and thus a faster rate of
ES reaction for the enzyme-catalyzed
Catalyzed Reaction S P reaction.
E + S ES S P
Reaction Progress
ES P + E
Reaction Progress
Key:
S = substrate
E = enzyme Enzyme-catalyzed reaction Uncatalyzed reaction
ES = enzyme-substrate complex
P = product

Substrate Binding Enzyme Activity

The Active Site The Native Structure
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.

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
Acetylcholinesterase catalyst.
HIV Protease

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 Case Study Acetylcholine
Acetylcholinesterase A Neurotransmitter

CH3 :O:
•Essential for nerve transmission at neuromuscular + ..
junctions (nerve-muscle connections) H3C N CH2 CH2 O
.. C CH3

•Removes excess acetylcholine (neurotransmitter) CH3

Ester Group
from synapse allowing neuron to reload and fire Ammonium Group
next nerve impulse.
•Target of nerve agents (Sarin, Tabun, Soman, etc) 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

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)
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).
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 O Histidine 440 Inhibitor

+
H3C N CH 2 CH 2 O C CH 3 + H 2O

CH 3 Acetylcholine
CH 3 O Serine 200
+
H3C N CH2 CH 2 O H + H O C CH 3

CH 3
Glutamate 199

These three amino acids, the catalytic triad,

are located at the active site and play a crucial
role in catalysis.

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 Nerve Agents Nerve Agents
Nerve agents work by reacting with the OH group Inhibition of Acetylcholinesterase

of the active-site serine that is required for catalytic Active

Site Sarin
activity. This disables (inhibits) the enzyme. O O
Sarin Soman VX ser CH2 F P CH3 ser CH2 O P CH3 + HF
O O O ..:
HO O O
F P CH3 F P CH3 CH3CH2 O P CH3 CH CH3 CH CH3
O O S
CH3 CH3
H3C CH CH3 HC CH3 CH2
Inactivated Enzyme
H3C C CH3 H3C CH N CH CH3
CH3 CH3 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