title: Dynamic simulation of pollutant effects on the threonine pathway in Escherichia coli.
abstract: The enzymatic activities of threonine pathway in Escherichia coli are sensitive to pollutants such as cadmium, copper and mercury, which, even at low concentration, can substantially decrease or even block the pathway at several steps. Our aim was to investigate the complex effects on a metabolic pathway of such general enzyme inhibitors with several sites of action, using a previously developed computer simulation of the pathway. For this purpose, the inhibition parameters were experimentally determined and incorporated in the model. The calculation of the flux control coefficient distribution between the five steps of the threonine pathway showed that control remains shared between the three first steps under most inhibition conditions. Response coefficient analysis shows that the inhibition of aspartate semialdehyde dehydrogenase is quantitatively dominant in most circumstances.
authors.affiliation: INSERM EMI 9929 & université Bordeaux-2, 146, rue Léo-Saignat, 33076 Bordeaux, France. christophe.chassagnole@insa-tlse.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Chassagnole
authors.forename: Eric
authors.initials: E
authors.lastname: Quentin
authors.forename: David A
authors.initials: DA
authors.lastname: Fell
authors.forename: Pedro
authors.initials: P
authors.lastname: de Atauri
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mazat
mesh_terms: D001223:Aspartate-Semialdehyde Dehydrogenase / Q000037:antagonists & inhibitors; D002104:Cadmium / Q000494:pharmacology; D003198:Computer Simulation; D003300:Copper / Q000494:pharmacology; D004785:Environmental Pollutants / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008628:Mercury / Q000494:pharmacology; D008954:Models, Biological; D013912:Threonine / Q000378:metabolism*
chemical_list: D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D002104:Cadmium; D013912:Threonine; D003300:Copper; D001223:Aspartate-Semialdehyde Dehydrogenase; D008628:Mercury