%0 Journal Article
%T Towards a genome-scale kinetic model of cellular metabolism
%A Kieran Smallbone
%A Evangelos Simeonidis
%A Neil Swainston
%A Pedro Mendes
%J BMC Systems Biology
%D 2010
%I BioMed Central
%R 10.1186/1752-0509-4-6
%X We describe a method for building a parameterized genome-scale kinetic model of a metabolic network. Simplified linlog kinetics are used and the parameters are extracted from a kinetic model repository. We demonstrate our methodology by applying it to yeast metabolism. The resultant model has 956 metabolic reactions involving 820 metabolites, and, whilst approximative, has considerably broader remit than any existing models of its type. Control analysis is used to identify key steps within the system.Our modelling framework may be considered a stepping-stone toward the long-term goal of a fully-parameterized model of yeast metabolism. The model is available in SBML format from the BioModels database (BioModels ID: MODEL1001200000) and at http://www.mcisb.org/resources/genomescale/ webcite.Recent advances in genome sequencing techniques and bioinformatic analyses have led to an explosion of systems-wide biological data. In turn, the reconstruction of genome-scale networks for micro-organisms has become possible. Whilst the first stoichiometric models were limited to the central metabolic pathways, later efforts such as iFF708 [1] and iND750 [2] were much more comprehensive. A recent community-driven reaction network for S. cerevisiae (bakers' yeast) consists of 1761 reactions and 1168 metabolites [3].The ability to analyse, interpret and ultimately predict cellular behaviour is a long sought-after goal. The genome sequencing projects are defining the molecular components within the cell, but describing their integrated function will be a challenging task. Ideally, one would like to use enzyme kinetics to characterize fully the mechanics of each reaction, in terms of how changes in metabolite concentrations affect local reaction rates. However, a considerable amount of data and effort is required to parameterize even a small mechanistic model; the determination of such parameters is costly and time-consuming, and moreover much of the required information may be diffic
%U http://www.biomedcentral.com/1752-0509/4/6