Glycolysis and Flux Control

Central metabolism of carbohydrates uses the Embden-Meyerhof-Parnas (EMP), pentose phosphate (PP), and Entner-Doudoroff (ED) pathways. This review reviews the biological roles of the enzymes and genes of these three pathways of E. coli. Glucose, pentoses, and gluconate are primarily discussed as the initial substrates of the three pathways, respectively. The genetic and allosteric regulatory mechanisms of glycolysis and the factors that affect metabolic flux through the pathways are considered here. Despite the fact that a lot of information on each of the reaction steps has been accumulated over the years for E. coli, surprisingly little quantitative information has been integrated to analyze glycolysis as a system. Therefore, the review presents a detailed description of each of the catalytic steps by a systemic approach. It considers both structural and kinetic aspects. Models that include kinetic information of the reaction steps will always contain the reaction stoichiometry and therefore follow the structural constraints, but in addition to these also kinetic rate laws must be fulfilled. The kinetic information obtained on isolated enzymes can be integrated using computer models to simulate behavior of the reaction network formed by these enzymes. Successful examples of such approaches are the modeling of glycolysis in S. cerevisiae, the parasite Trypanosoma brucei, and the red blood cell. With the rapid developments in the field of Systems Biology many new methods have been and will be developed, for experimental and theoretical approaches, and the authors expect that these will be applied to E. coli glycolysis in the near future.