Chemical Kinetics, Mechanisms

• We will derive the rate of an overall reaction

from a system of elementary reaction rates, a
mechanism.
• The stoichiometry of an elementary reaction
defines the concentration dependence of the
rate expression.
• The quasi-steady state assumption and
equilibrium assumption will minimize the number
of rate constants in a rate expression.

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Idea is to find some linear combination of the elementary reactions to
produce the stoichiometry of the overall observed reaction. If this cannot
be done, the proposed reaction mechanism is not valid.

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Elementary reactions - characteristics

•Proceeds as written with no identifiable intermediates. This

implies a collision.

•Rate depends on the concentrations of the reactants…the

probability of collision.

• Inherently reversible, Tolman’s principle. Reverse reaction

must be possible based on energy, symmetry and steric
considerations.

•Transition state theory – if during a vibration the transition

state falls apart, it may become either reactant or product.
The step to transition state is so fast that we assume
equilibration. ( e.g. molecular motion happens on a scale of11
1013/sec.)
• Do we have to solve a system of ODE’s
for a given mechanism to know something
about the reaction kinetics, or is there a
way to “estimate” kinetic information which
can be handled offline?

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 Michaelis Menten Kinetics, Example

Verify that the proposed mechanism can give a

kinetic expression in which, when CS is very
large, rate is linear with CE0

E= enzyme
S=substrate
ES= bound substrate
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P=product
• QSSA: ES is a steady state intermediate
dCES
= 0 = k1CE CS − k2CES − k3CES
dt
dCP
RP = = k3CES
dt
• Mass balance
CE0 = CE + CES 38
From QSSA equation:
k1(CE)(CS) = (k2 + k3)(CES)

Substitute mass balance:

k1(CEo-CES)(CS) = (k2 + k3)(CES)

Distribute:
k1(CEo)(CS) - k1(CES)(CS) = (k2 + k3)(CES)

Collect ES terms:
k1(CEo)(CS) = (k2 + k3)(CES) + k1(CES)(CS)
k1(CEo)(CS) = CES (k2 + k3 + k1S)

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 k1CE0 CS
CES =
k2 + k3 + k1CS

CE0 CS
CES =
k 2 + k3
+ CS
k1

Now we can return to the original production equation for P, and express in
terms that do not involve concentrations of intermediates.

dCP k3CE0 CS k 2 + k3
= k3CES = ; where K M =
dt K M + CS k1
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Verification of Michaelis-Menten
Kinetics
• When S is very large, rate goes to a
maximal velocity given by…
RP ~ k3CE0

• If k2>>k3; then KM has a value =

dissociation constant.

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 More complicated biochemical
reaction
• Not all reactions can be characterized so
simply as a simple substrate interacting
with an enzyme to form an ES complex,
which then turns over to form product.
Sometimes, intermediates form.

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H. Jacubowski, St. Johns Univ. MN

• For example, a substrate S might interact
with E to form a complex, which then is
cleaved to products P and Q. Q is
released from the enzyme, but P might
stay covalently attached.

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• This happens often in the hydrolytic cleavage of a
peptide bond by a protease, when an activated
nucleophile like Ser reacts with the sessile peptide bond
in a nucleophilic substitution reaction, releasing the
amine end of the former peptide bond as the leaving
group, while the carboxy end of the peptide bond
remains bonded to the Ser as an Ser-acyl intermediate.
Water then enters and cleaves the acyl intermediate,
freeing the carboxyl end of the original peptide bond.

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• Assume rapid equilibrium in first step,
characterized by equilibrium constant KS.
• Assume E-P is an intermediate at steady
state.
• The second reaction is the rate limiting
step.
• Verify:

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