Kinetic model of functioning and regulation of Escherichia coli isocitrate dehydrogenase
To describe published experimental data on the functioning of E. coli isocitrate dehydrogenase (IDH), a Rapid Equilibrium Random Bi Ter mechanism involving the formation of two dead-end enzyme complexes is proposed and a kinetic model of enzyme functioning is constructed. The enzyme is shown to be regulated through reversible phosphorylation by IDH kinase/phosphatase; the latter, in its turn, is controlled by IDH substrates and also by a number of central metabolites—pyruvate, 3-phosphoglycerate, and AMP—reflecting the energy demand of the cell. Using the model, it is shown that an increase in the concentration of the above effectors raises the fraction of active IDH and thus enhances the Krebs cycle flux. The ratio between the free and the phosphorylated forms of IDH is more sensitive to AMP, NADP, and isocitrate than to pyruvate and 3-phosphoglycerate. The model also predicts changes in the ratio between phosphorylated and active forms of IDH in the Krebs cycle that occur with a change in the energy and biosynthetic loads on E. coli cells.
Key wordsKrebs cycle isocitrate dehydrogenase kinetic model
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- 1.F. C. Neidhardt, Cell. Mol. Biol. 1, 3 (1987).Google Scholar
- 3.H. G. Nimmo, Biochem. J. 234, 317 (1986).Google Scholar
- 8.A. Cornish-Bowden, Principles of Enzyme Kinetics (Butterworths, London, 1976; Mir, Moscow, 1979).Google Scholar
- 9.O. V. Demin, I. I. Goryanin, S. Dronov, and G. V. Lebedeva, Biokhimiya 69, 1625 (2004).Google Scholar
- 11.M. L. Uhr, V. W. Thompson, and W. W. Cleland, J. Biol. Chem. 249, 2920 (1974).Google Scholar
- 12.C. S. Stueland, K. R. Eck, Stieglbauer, and D. C. LaPorte, J. Biol. Chem. 262, 16095 (1987).Google Scholar
- 13.C. S. Stueland, K. Gorden, and D. C. LaPorte, J. Biol. Chem. 263, 19475 (1988).Google Scholar
- 14.K. Walsh, and D. E. Koshland, Jr., J. Biol. Chem. 259, 9646 (1984).Google Scholar
- 15.O. H. Lowry, J. Carter, J. B. Ward, and L. Glaser, J. Biol. Chem. 246, 6511 (1971).Google Scholar
- 16.K. B. Andersen, and K. von Meyenburg, J. Biol. Chem. 252, 4151 (1977).Google Scholar