Biology Reference
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label of systems biology. Among these are the current models of motor regulation
in
E. coli
, signaling pathways, and complex biosynthetic and other metabolic
pathways (Kitano 2002c, Part IV; Kholodenko, 2006). Like the earlier models,
they start from a physiological capacity that is analyzed by molecular-biological
methods, the model being built bottom-up from these data. The main difference
compared to the earlier version is that the models provide more and more
details. In most cases, this does not mean that the models become more fine-
grained with respect to components of pathways already considered in the older
models. As discussed in Section 3, those models already referred to the single
species of molecules involved in a reaction chain and accounted for their kinetic
parameters. The main way in which more details are considered, then, is that
additional components at the periphery of the metabolic pathways are integrated
into the model so that the reaction networks grow. This is the case, for instance,
with signaling networks, which were formerly restricted to the size of, say, a
single G-protein signaling pathway, and perhaps its coupling to the activation of
the Ca
2
+
-pathway. The new models of signaling pathways represent a network
that incorporates about four times as many components (Kholodenko, 2006;
Palsson, 2006, p. 85). In the case of chemotactic motor response of
E. coli
,
models now consider the gene regulatory pathways in addition to the processes
that account for the response in a certain physiological state (Bourret & Stock,
2002). With respect to metabolic pathways, models now combine within one
network what were previously considered separate pathways among which at
best some crosstalk might have existed (Thiele et al., 2005). The model of the
mammalian circadian clock was refined and now represents a network of five
genes and their gene products (Leloup & Goldbeter, 2003).
At first glimpse, and keeping in mind that the detailed
Biochemical pathways
map was already available in 1974, it is astonishing that more detailed models
of the sort described have been developed only recently. In its first edition, the
map depicted 760 enzymes and the metabolic pathways they are involved in.
This was about one third of the enzymes known at the time and covered most
of the core metabolism of the eukaryotic cell (Michal, 1982). However, there
is a crucial difference. Although the old maps of metabolic pathways depicted
all the known enzymes, reactions, and regulatory relationships, this was a static
depiction of the metabolic network that did not allow to calculate its dynamics.
In contrast, systems biological models of such networks aim for computability of
the network dynamics. In this sense, they are the successors of dynamic models
of restricted metabolic pathways. These models are still created bottom-up and
are compiled from data about single enzymes with known kinetic constants.
What is new is the large amount of structural data that are considered in the
model. In this sense, these systems biological models merge the old rationale
of modeling regulatory pathways that were comparatively data-poor with richer
molecular data.
