Metabolic Networks - Biological Networks - page 166

8.2. Relevant Biological Feature from Network Wiring
8.2.1. Network topology and effect of mutations
From a purely topological point of view, each node of a network is uniquely
defined by its position in the graph. Obviously, when dealing with
experimentally derived and not abstract networks, each node has a name (a
particular gene, protein, metabolite) and the same is true for the edges. However,
if we are interested in discovering what can be inferred solely from topological
information, we should try and predict some relevant features of the studied
organism without relying on the particular 'nature' of nodes and edges, but only
taking into consideration their connectivity pattern. In other terms, all the
properties relative to each node (edge) must be derived only by its pattern of
relations. We checked for the possibility to derive, from purely topological
information on the metabolic network of Saccharomyces cerevisiae , the lethal
character of genetic mutations.
The metabolic network of microorganisms, at odds with different biological
networks like protein-protein interaction network or genetic regulation network,
is very well understood and characterized. It corresponds to those Boheringer's
'Charts of Metabolism', pinned on the walls of almost every biochemistry
laboratory in the world, having enzymatic reactions as edges and metabolites as
nodes. Since an enzymatic reaction is catalyzed by one or more enzymes, an arc
can also represent the enzyme(s) involved in the reaction. This opens the way to
a straightforward analysis of the possibility to derive biologically meaningful
features from network topology: the elimination of an enzyme by means of a
knock-out experiment implies the elimination from the network of the edge (or
edges since, as reported above, the same enzyme can catalyze several
biochemical reactions) corresponding to that particular enzyme.
If it is possible to pick up a connectivity descriptor able to unequivocally
define essential enzymes (those enzymes whose lack provokes the yeast death)
we can safely assume the biological relevance of the metabolism 'wiring
structure', irrespective of the knowledge of the specific nature of the involved
enzymes. This should correspond to the possibility to define the essentiality of
single enzymes for the yeast life in terms of metabolic network topology. This
also implies that the relevance of a specific enzyme derives from its role in a
global architecture that is the 'effective system' that carries out the metabolic
work in the cell. In other words, the possibility to predict the essential character
of a specific enzyme on the sole basis of its pattern of connections in the