The mathematical model of the operation of the first enzyme of the Escherichia coli phosphotransferase system, EI, is proposed. Parameters of the kinetic model describing the operation of EI under different conditions are identified on the basis of a large amount of known experimental data. The verified model is employed to predict modes of operation of EI under both in vivo physiological conditions and in vitro nonphysiological conditions. The model predicts that under in vivo physiological conditions, the rate of phosphotransfer from EI to the second protein of the phosphotransferase system HPr by the dimer is much higher than by the monomer. A hypothesis is proposed on the basis of calculations that the transfer by a monomer plays a role in the regulation of chemotaxis. At submicromolar pyruvate concentration, the model predicts nonmonotonic dependence of the phosphotransfer rate on the substrate (PEP) concentration. 1. Introduction The phosphotransferase system (PTS) of Escherichia coli transfers carbohydrates into the cell with simultaneous phosphorylation [1, 2]. This process operates in several steps: from the PEP, a phosphate group is transferred to EI, then to HPr, the next enzyme of the system, which, in turn, delivers a phosphate group to the enzymes EIIA and EIICB, which are specific for different carbohydrates. The glucose uptake is carried out by EIIAGlc and EIICBGlc. The membrane-spanning enzyme EIICBGlc is capable of catalyzing the transfer of a phosphate group from EIIAGlc to a molecule of the relevant carbohydrate in parallel with transfer of the carbohydrate to cytoplasm. Besides the transport and phosphorylation of carbohydrates, PTS regulates metabolism of other carbohydrates, which are not PTS substrates (lactose, melibiose, etc.) [2]. In particular, the EIIAGlc molecule, in addition to glucose phosphorylation, is involved in catabolite repression: in the absence of PTS-substrates, EIIAGlc is mainly observed in the phosphorylated form, which activates adenylate-cyclase, and thus increases the intracellular level of c-AMP, which has an effect on the expression of a great number of genes [2]. In the presence of PTS-substrates EIIAGlc is dephosphorylated. Nonphosphorylated EIIAGlc takes part in a phenomenon called “inducer exclusion”. In fact, Nonphosphorylated EIIAGlc is able to bind to and inhibit proteins essential in the metabolism of several carbohydrates (e.g., lactose, melibiose, maltose and glycerol) [3]. It was also shown that growth on many non-PTS carbon sources caused dephosphorylation of EIIAGlc and that phosphorylation
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