Coordination of Central Metabolix Fluxes in Microbes

Speaker:      Uwe Sauer

                     Head of the Institute for Molecular System’s Biology, ETH Zurich

Subject:       Coordination of central metabolix fluxes in microbes

Location:     Bionanoscience Department, TU Delft

Date:            Thursday, 4 december 2014, 16:00-17:00

 Author: Jasper Veerman

Uwe Sauer is interested in the long term coordination of metabolism. For the past years, there seemed to be the general misconception that metabolism is just the workhorse of the cell. Metabolites turn out to also be important in, for example, intracellular signaling. Using labeled carbon atoms, Uwe Sauer’s group studies fluxes in the cell. This method allows to look at a molecule’s history. Combining this with quantitative physiology allows for modeling of the fluxes in the cell.

Using the above-mentioned approach, he studied the change in enzyme as compared to the flux difference in steady state. If these differences scale 1:1, then the change in enzyme is totally responsible for increased or decreased fluxes in the pathways (like . glucose catabolism). These cases mostly relate to full transcriptional regulation of fluxes. However, these cases are rare. In most cases – over 90% –  we need additional factors, for example metabolic influences, to explain the change in fluxes.

In addition, the group studied active, dynamic allosteric interactions (ligand binding that changes the conformation of the active site of the enzyme). Due to their direct regulation of enzyme activity, they should dominate over transcription. By implementing allosteric interactions into the model that was already present, the model fitted the experimental results somewhat better. Allosteric interactions appear to account for some of the observed behavior of the pathways. However, other influences are still to be added for proper description of the pathways. Looking at cell metabolism is a good place to start.

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