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metabolic network tells us the metabolic network wiring it is not only a way of
formalization but the image in light of a biological entity.
In the graphic representation of the
Saccharomyces cerevisiae
metabolic
network shown in Fig. 8.3, nodes represent metabolites, and arcs indicate
enzymes involved in the reaction necessary to synthesize a product from a
reactant. Yellow bars show where essential enzymes are located. Essential
enzymes are those whose lack provokes lethal effects for the yeast. Nodes
colored in blue, light blue, violet and green belong to the strongly connected
components of the network. These components constitute the cores of the
network and all of the nodes belonging to one of them can reach one another
because they are fully connected.
In order to base our analysis on reliable data we considered only the
knockouts in which there was a substantial agreement between different
experimental evidences, namely a specific enzyme is considered as essential, and
consequently the correspondent arcs in the network representation are deleted, if
at least the 75% of genes coding for that particular enzyme were demonstrated to
be lethal in the knocked out organism. If a specific reaction is catalysed by
multiple enzymes, the corresponding arc in the graph is deleted if the above
condition is fulfilled for all the enzymes involved. These very stringent
conditions allowed us to select only 37 lethal mutations out of the 412 relative to
enzymes involved in metabolism, reported in the Stanford repository
(http://www-equence.stanford.edu/group/yeast_deletion_project/deletions3.html).
The main effects of inhibitions of essential enzymes can be briefly grouped
into the following categories (see also Fig. 8.4):
•
Preventing the connection between the nodes at the ends of the eliminated
arc: no other path is available to restore the previous connection (37/37
essential enzymes).
•
Isolating a pathway from the rest of the network (29/37 essential enzymes,
Panel a).
•
Destroying the full connectivity in a strongly connected component (7/37
essential enzymes, corresponding to 4/37 in the giant set and 3/37 in the
minor SCCs, Panel b).
•
Creating a new smaller SCC from another one (1/37 essential enzymes,
Panel c).
•
Disrupting a cluster of nodes in the IS compartment (16/37 essential
enzymes, Panel d).
