While cAMP∙Crp controls many operons for uptake systems and peripheral metabolic enzymes as well as for enzymes of the TCA and of the respiratory chain, expression of the genes encoding enzymes of glycolysis generally is not influenced by cAMP∙Crp. Several of these genes are influenced by another PTS related regulator FruR or Cra [7]. FruR represents the repressor for the fru operon encoding

the components of the fructose PTS as well as a 1-phosphofructokinase. In addition to its function as a specific regulator of the fru operon, FruR acts as an Protein Tyrosine Kinase inhibitor important regulator controlling or coordinating the fluxes of glycolysis and gluconeogenesis. It responds to the concentration of fructose-1-phosphate Inhibitors,research,lifescience,medical and fructose-1,6-bisphosphate in the cells [8]. Interestingly, fructose-1,6-bisphosphate is important for controlling an important point in glycolysis as it is an allosteric activator of pyruvate kinase [9], the enzyme that converts PEP Inhibitors,research,lifescience,medical to pyruvate. The same conversion is also performed by the PTS (Figure 2). Although these regulations have been characterized by different experimental approaches, a good understanding of the interplay of these regulations Inhibitors,research,lifescience,medical and of the overall effect on the fluxes in central metabolism is

still lacking. 2. Results and Discussion 2.1. Structural Analysis of the Glycolysis Core Model The model describes the steady state behavior of important metabolites of glycolysis in E. coli. Important components and starting points Inhibitors,research,lifescience,medical for signalling pathways are fructose-1,6-bisphosphate (ligand for transcription factor FruR), PEP and pyruvate (both determine the degree of phosphorylation of protein EIIA of the PTS). In addition, glucose 6-phosphate is taken into account as entry component into glycolysis. The stoichiometric equations are as follows: (1) with glucose 6-phosphate G6P, phosphoenolpyruvate PEP, pyruvate Prv, and a lumped Inhibitors,research,lifescience,medical component of the PTS, enzyme IIA EIIA; E stands for the respective enzyme, r for the rate. The equations consider

that a carbohydrate (PTS as well as non-PTS sugars) is fed into glycolysis via glucose-6-phosphate. The carbohydrate is metabolized by a sequence of steps with pyruvate as the final component. In reaction rgly reversible CYTH4 reaction steps catalyzed by the enzymes fructose bisphosphate aldolase, triose phosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phophoglycerate mutase and enolase are lumped (Egly). First the influence of regulation of gene expression and of allosteric control is studied. Based on the approach described in Material and Methods, the derivatives for the metabolites are calculated. Matrix D has the following entries: (2) where the rows consider rpfk, rgly, rpyk, and rpdh, and the columns consider G6P, F16BP, PEP, and Prv.