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Enzo Marinari |
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Università di Roma "la Sapienza" |
Abstract
Understanding the organization of reaction fluxes in
cellular metabolism from the stoichiometry and the topology of the
underlying biochemical network is a central issue in systems biology.
In this task, it is important to devise reasonable approximation
schemes that rely on the stoichiometric data only, because full-scale
kinetic approaches are computationally affordable only for small
networks (e.g. red blood cells, about 50 reactions). Methods commonly
employed are based on finding the stationary flux configurations that
satisfy mass-balance conditions for metabolites, often coupling them
to local optimization rules (e.g. maximization of biomass production)
to reduce the size of the solution space to a single point. Such
methods have been widely applied and have proven able to reproduce
experimental findings for relatively simple organisms in specific
conditions. Here we define and study a constraint-based model of
cellular metabolism where neither mass balance nor flux stationarity
are postulated, and where the relevant flux configurations optimize
the global growth of the system. In the case of {\it E. coli}, steady
flux states are recovered as solutions, though mass-balance conditions
are violated for some metabolites, implying a non-zero net production
of the latter. Such solutions furthermore turn out to provide the
correct statistics of fluxes for the bacterium {\it E. coli} in
different environments and compare well with the available
experimental evidence on individual fluxes. Conserved metabolic pools
play a key role in determining growth rate and flux variability.
Finally, we are able to connect phenomenological gene essentiality
with `frozen' fluxes (i.e. fluxes with smaller allowed variability) in
" E. coli" metabolism.