Comparison of Michaelis-Menten Expression to the Full

Mechanism
Biochemical Engineering

Problem Statement: Consider the following enzyme reaction mechanism:

k1 k2
E + S <------> ES ------> E + P
k-1
where the rate constants are: k1=10, k-1=10, and k2=1. Initially charge the bioreactor with
an equal amount of enzyme and substrate of 1 unit each. Find the time at which the
substrate concentration in the reactor drops to one half of the initial charge. Compare a)
the result obtained by directly integrating the dynamic equations derived from elemental
reaction mechanism against b) that from the Michaelis-Menten rate expression.

Solution:

The following Mathcad worksheet solves the specific problem with the given set of
parameters.

Comparison of Michaelis-Menten Expression to the Full Mechanism

 Just the Simulation Graph (hw4-3a.gif)

 Snapshot of Mathcad Screen (hw4-3.gif)
 Mathcad File (hw4-3.mcd)

The following files, albeit written slightly differently or having a different set of model
parameters, solve an identical set of ODEs. They demonstrate different ways of using
Mathcad.

Integrate ODEs Arising from Enzyme Kinetic Mechanisms

 /w "rkfixed"
o Snapshot of Mathcad Screen (ench482b.gif)
o Mathcad File (ench482b.mcd)
 Slightly longer but clearer
o Snapshot of Mathcad Screen (ench482c.gif)
o Mathcad File (ench482c.mcd)
 /w Euler's Method
o Snapshot of Mathcad Screen (ench482d.gif)
o Mathcad File (ench482d.mcd)
 Heavy Enzyme Loading (just the simulation graph from running one of the above
programs) (mm1.gif)
The simulations on a closed batch reactor clearly shows that the Michaelis-Menten
expression is valid when E0<<S0 and that it is invalid when E0~S0. However, it is
important to realize that we are simulating a batch reactor in the next exercise, not a
biological cell. The Michaelis-Menten expression is routinely used to describe enzymatic
reactions inside cells despite that the relationship E0<<S0 does not always hold. This is
because a cell is not a closed batch system. There is constant exchange of materials with
the surrounding, and we do not start up a cell at t=0 with no ES complex. If you provide
more appropriate conditions and simulate a biological cell rather than a batch reactor, you
should see that the Michaelis-Menten expression remains a good approximation even
when E0~S0. (Question: how would you modify the equations to simulate a cell?)

See Michaelis-Menten Kinetics with enzyme deactivation, when the enzyme activity is
time-dependent due to deactivation.