Case Study: Immobilized enzyme packed bed reactor

Enzymes are proteins in the body whose main functions are to catalyze a host of life-sustaining chemical
reactions, such as breaking down food into its primary components, e.g. proteins into aminoacids,
converting glucose to CO2 and H2O, synthesizing molecular components of cells, enabling transcription
and translation of genes, and so on. Enzymes have tremendous specificity for the substrate acted upon and
the reaction catalyzed. The rate of reaction r for an enzyme-catalyzed reaction such as


where E is the enzyme, S is the substrate, and P is the product, is commonly described using
MichaelisMenten kinetics:
where
S is the substrate concentration,
R
max
is the maximum reaction rate for a particular enzyme concentration E,
K
m
is the Michealis constant, equal to the substrate concentration at which the reaction rate is half of the
maximum rate.
Equation (5.29) can be integrated to yield an analytical relationship between the substrate concentration
and time as follows:
Enzymes can be produced (using genetic engineering techniques), purified, and then used ex vivo in a
suitably designed contacting device to catalyze similar reactions when placed in a conducive
physiological environment, such as at body temperature and favorable pH. Often enzymes are
immobilized on a support structure within the contacting equipment rather than kept free in solution.
This is advantageous for several reasons, such as (1) ease of separation of the contact stream from the
enzyme (the exiting stream must be cleared of enzyme if it is introduced into the body) and (2) reduced
loss of enzymes, which is especially important when the process is expensive.
In certain diseased conditions, the inefficient breakdown of a specific accumulating molecular entity can
pose a threat to the body since abnormally high concentration levels of the non-decomposed substrate
may be toxic to certain body tissues. In such cases the use of an immobilized enzyme reactor to catalyze
the breakdown reaction extracorporeally may be of therapeutic benefit. There are several options
available for the type of contacting device and contacting scheme used to carry out the reaction process. A
packed bed is a commonly used reactor configuration in which the catalyst particles are dispersed on a
support structure throughout the reactor and an aqueous stream containing the substrate continuously
passes through the reactor (McCabe et al., (2004) provides an introduction to packed bed columns).

A prototype immobilized enzyme packed bed reactor has been designed whose function is to degrade a
metabolite X that is normally processed by the liver except in cases of liver disease or liver malfunction.
Accumulation of X in the body prevents functioning of certain cell types in the body.
Enzyme AZX is a patented enzyme that is immobilized within inert pellet particles contained in the
reactor (Figure 5.12) and degrades X according to MichaelisMenten kinetics (Equation (5.29)). A simple
mass balance over the reactor based on certain simplifying assumptions produces the following design
equation for the reactor (Fournier, 2007):

where

S
feed
is the concentration of
substrate in the feed stream,
S
out
is the concentration of
substrate in the exiting stream,
K is the partition coefficient and is
the ratio of the substrate
concentration inside the pellet
pores at the surface to the substrate
concentration in the external fluid
at the pellet surface, Km is the Michaelis constant (see Equation (5.29)),
A
c
is the reactor column cross-sectional area,
L is the reactor length,
is the porosity of the column (fractional volume not occupied by pellets),
R
max
is the maximum reaction velocity (see Equation (5.29)),
Q is the flowrate of the feed stream into the plug flow packed bed reactor, is the reaction efficiency that
measures the effect of mass transfer resistance on reaction rate.

We rewrite Equation (5.31) as follows:




and solve using Newtons method. The derivative of f(S
out
) specified in Equation (5.32) is given by