Environmental Engineering Reference
In-Depth Information
levels through all the reactions necessary to con-
vert substrates to products, to balance all cofac-
tor pools, and to secrete any byproducts needed
to maintain the network in a homeostatic state.
The sets of extreme pathways studied here lead
to the synthesis of a target product, such as an
individual amino acid or all the protein in a cell.
Therefore, each extreme pathway in the set cor-
responds to a complete flux map that synthesizes
the target product within the metabolic network.
Extreme pathways are so named because they are
the edges of a solution space and thus character-
ize the extreme functions of the network. The ex-
treme pathways can be thought of as generating a
convex cone in high-dimensional space, circum-
scribing all possible steady-state metabolic phe-
notypes. (Papin et al.
2002
)
It should be noted that the extreme pathways
are an irreducible, non-redundant subset of el-
ementary modes (Pfeiffer et al.
1999
; Schuster
et al.
1999
,
2000
). Elementary modes for a given
network are more numerous than the extreme
pathways, but can all be represented by non-neg-
ative, linear combinations of the extreme path-
ways.
Type I
extreme pathways have exchange
fluxes that cross system boundaries, and repre-
sent primary metabolic pathways. These extreme
pathways detail the conversion of substrates into
products and byproducts.
Type II
extreme pathways also have exchange
fluxes that cross system boundaries, but these
exchange fluxes only correspond to “currency”
metabolites, such as ATP, NADH and so forth.
Type II
pathways can be through of as “futile”
cycles, and must proceed “downhill” in terms of
free energy.
Type III
extreme pathways have no active ex-
change fluxes, and therefore represent internal
cycles. Based upon thermodynamics, these cy-
cles cannot be active because there is no energy
source to drive them. Thus, these type III extreme
pathways can be eliminated from the convex basis
without loss of phenotypic potential. (http://gcrg.
ucsd.edu/sites/default/files/Attachments/Images/
classes/taiwan_notes/5_slides_expa.pdf).
3.2.3
Pathway Tool
The Pathway Tools are the software environment
for the quality production of model-organism
databases (MODs), and are also reusable. The
Model-Organism Databases formed are called
pathways/genome databases (PGDB). Informa-
tion related to genes, proteins and the genetic and
metabolic networks of an organism is stored in
the PGDB. The Pathway Tool gives two different
modalities for interacting with a PGDB:
3.2.2
Types of Extreme Pathways
Extreme pathways can be classified into three
types, based upon the metabolites that enter and
leave the particular network, known as exchange
fluxes (Fig.
3.4
).
Fig. 3.4
Showing the types of extreme pathways based on their exchange fluxes. (Reproduced from
http://www2.bio.
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