34
Chapter 2
ATP is not the only compound involved in coupling catabolism and anabolism tightly together.
Also NADH and NADPH have small turnover times, and the cell must also exercise a strict control
of the level of these compounds. The tight control of these co-factors may be represented by the
following variables that are analogous with the energy charge (Ingraham
et ai,
1983):
Catabolic reduction charge = ?------[A£4D//]------
[n a d h ]+[n a d *\
(
2
.
10
)
Anabolic reduction charge = T
-------
[n a d p h }+ [n a d p +\
(
2
.
1 1
)
In growing cells the catabolic reduction charge is maintained at a low level of 0.03-0.07 and the
anabolic reduction charge at the higher level of 0.4-0.5. In the catabolism, NAD+ is a substrate (and
NADH is a product), and this explains why catabolic reduction charge is controlled at a low level
when these reactions are to proceed. NADPH, on the other hand, is a substrate for the anabolic
reactions, and the anabolic reduction charge therefore has to be controlled at a higher level. The
different levels of the two reduction charges explain the necessity for two different co-enzymes in
the cell - they have different functions, and therefore have to be controlled at different levels in
order to ensure proper function of the cell during growth.
The number of building blocks necessary for cellular synthesis varies between 75 and 100, and
these are all synthesized from 12 precursor metabolites (see Table 2.4), which are intermediates in
the fueling reactions (or the catabolism). Thus, the supply of these precursor metabolites further
links the catabolism and the anabolism. When intermediates in the TCA cycle are used for
biosynthesis, it is necessary to replenish these compounds since the TCA cycle activity would
otherwise decline. The reactions involved are called the
anaplerotic pathways,
and the most
important pathways are:
Carboxylation reactions, where either pyruvate or phosphoenolpyruvate are carboxylated
leading to formation of the TCA-cycle intermediate oxaloacetate (which at the same time is
a precursor metabolite). Carboxylation of pyruvate is illustrated in Fig. 2.5.
The glyoxylate cycle, which involves several steps of the TCA cycle and two additional
reaction steps (see Fig. 2.5). In these steps the TCA cycle intermediate isocitrate is cleaved
to succinate (another TCA cycle intermediate) and glyoxylate and subsequently glyoxylate
reacts with acetyl-CoA to form malate (also a TCA cycle intermediate). The glyoxylate
cycle allows for net synthesis of 4 carbon containing compounds from acetyl-CoA, and it
plays an important role when cells are growing on C2 carbon compounds such as acetate
and ethanol.
Clearly the formation of all the building blocks needed to synthesize a cell involves a large number
of reactions and often very long pathways are involved in the synthesis of a single building block.
To get an overview of biosynthetic pathways we therefore refer to standard biochemistry textbooks
or reaction databases available on the World Wide Web, e.g., www.genome adj jp .
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