5
Biochemical Reaction Networks
Evolution has resulted in a complex metabolic network to ensure the proper function of living cells.
In many biotech processes the metabolic networks of living cells are exploited for production of
desired compounds. As discussed in Chapter 2 the metabolism can roughly be divided into
catabolism and anabolism. The catabolism ensures supply of Gibbs free energy in the form of high-
energy phosphate bonds in ATP, co-factors like NADH and NADPH, and a set of 12 precursor
metabolites - everything that is needed for biosynthesis of cell mass. In Chapter 3 we lumped the
myriad of reactions in the metabolic network into a single overall reaction - the black box model.
This is very useful when the aim is to check the overall balances of carbon flowing in and out of the
cell, but it does not supply any information about the processes occurring inside the cells. Clearly
the complexity increases when intracellular reactions are considered in the analysis, but as will be
discussed in this chapter there is a constant balancing of the formation and consumption of
intracellular metabolites, and this imposes a large number of constraints on the fluxes through the
different branches of the metabolic network. Thus, even though the complexity increases, the
degrees of freedom do not necessarily increase, and expansion of the analysis to include
intracellular reactions - in some cases lumped together into a few overall reactions - may in many
cases be very useful. In this chapter we are going to look into the basic concepts of metabolic
balancing (Section 5.1). In the rest of the chapter we will consider biochemical reaction models of
increasing complexity - first simple models balanced only with respect to ATP, NADH and
possibly NADPH (Section 5.2); thereafter simple metabolic networks where the metabolic network
is lumped into a few overall pathway routes (Section 5.3), and finally more complete metabolic
networks that permit a deeper analysis of the activities in the different branches of the metabolic
network at varying growth conditions (Section 5.4).
5.1 Basic Concepts
When calculating the fluxes through the different branches of a metabolic network we shall use
information about the net flows in and out of the cells, i.e. the net rate of production of substrates
and metabolic products that can be measured as described in section 3.1. These are the only
fluxes that can be directly measured, since it is not yet possible to measure fluxes within the cell.
If a cell is pulled apart in order to measure the enzyme activities the controls imposed on the
individual enzymes is lost, and the enzyme activity measured
in vitro
will therefore not say much
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