An integrated study of Threonine-pathway enzyme kinetics in Escherichia coli

Model Status

This model runs in COR and OpenCell and the units are consistent throughout. It is unknown whether it can recreate the published results, as there are no figures containing output of the complete model to compare it to. It is expected that if validation was carried out the model would be unable to recreate the published results, as some equations were missing from the paper and extrapolated from the reaction scheme.

Model Structure

ABSTRACT: We have determined the kinetic parameters of the individual steps of the threonine pathway from aspartate in Escherichia coli under a single set of experimental conditions chosen to be physiologically relevant. Our aim was to summarize the kinetic behaviour of each enzyme in a single tractable equation that takes into account the effect of the products as competitive inhibitors of the substrates in the forward reaction and also, when appropriate (e.g. near-equilibrium reactions), as substrates of the reverse reactions. Co-operative feedback inhibition by threonine and lysine was also included as necessary. We derived the simplest rate equations that describe the salient features of the enzymes in the physiological range of metabolite concentrations in order to incorporate them ultimately into a complete model of the threonine pathway, able to predict quantitatively the behaviour of the pathway under natural or engineered conditions.

The original paper reference is cited below:

An integrated study of threonine-pathway enzyme kinetics in Escherichia coli , Christophe Chassagnole, Badr Rais, Eric Quentin, David A. Fell and Jean-Pierre Mazat, 2001, Biochemical Journal , 356, 415-423. PubMed ID: 11368768

Threonine-synthesis pathway from aspartate in E. coli. The different steps are catalysed by aspartate kinases I and III (AK I and AK III), aspartate semialdehyde dehydrogenase (ASD), homoserine dehydrogenase (HDH), homoserine kinase (HK) and threonine synthase (TS). The abbreviations used are: asp, aspartate; aspp, beta-aspartyl phosphate; ASA, aspartic beta-semialdehyde; hs, homoserine; hsp, O-phospho-homoserine; thr, threonine and lys, lysine. Solid black lines represent the individual reaction steps of the pathway and the dashed red lines represent reaction inhibition by threonine and lysine.