Coordination of the dynamics of yeast sphingolipid metabolism during the diauxic shift

The approach uses two components: publicly available sets of expression data of sphingolipid genes and a recently developed Generalized Mass Action (GMA) mathematical model of the sphingolipid pathway. In one line of exploration, we analyze the sensitivity of the model with respect to enzyme activities, and thus gene expression. Complementary to this approach, we convert the gene expression data into changes in enzyme activities and then predict metabolic consequences by means of the mathematical model. It was found that most of the sensitivities in the model are low in magnitude, but that some stand out as relatively high. This information was then deployed to test whether the cell uses a few of the very sensitive pathway steps to mount a response or whether the control is distributed throughout the pathway. Pilot experiments confirm qualitatively and in part quantitatively the predictions of a group of metabolite simulations.The results indicate that yeast coordinates sphingolipid mediated changes during the diauxic shift through an array of small changes in many genes and enzymes, rather than relying on a strategy involving a few select genes with high sensitivity. This study also highlights a novel approach in coupling data mining with mathematical modeling in order to evaluate specific metabolic pathways.Yeast cells challenged by depletion of their preferred carbon sources in the surrounding medium begin using other available carbons for energy production. This switch, usually from glucose to ethanol and acetate, is known as the diauxic shift. It is not surprising that the diauxic shift constitutes a very complicated dynamic process that requires fine tuned coordination at the genomic and biochemical levels. At the genomic level, the switch to secondary non-fermentable carbon sources necessitates sweeping changes in gene regulation, which have been assessed with microarrays measured at a series of time points [1,2]Specifically about the time of diauxic shift, t