A Mathematical Model for Enzyme Clustering in Glucose Metabolism
Tuesday, May 29, 2018 - 3:10pm - 4:00pm
Sequential enzymes in glucose metabolism regulate glycolysis and gluconeogenesis in living cells. It has long been hypothesized that these enzymes form multienzyme complexes and control glucose flux. We have recently demonstrated that the rate-limiting enzymes in the cytoplasm are organized as a multienzyme complex, the glucosome, in at least three different sizes. Quantitative high-content imaging data support a hypothesis that the glucosome clusters regulate the direction of glucose flux between energy metabolism and building block biosynthesis in a cluster size-dependent manner. However, direct measurement of their functional contributions to cellular metabolism at subcellular levels has remained to be challenging. To support this finding, we develop a mathematical model using a system of differential equations, in which the association of the rate-limiting enzymes into multienzyme complexes is included as an essential element. We then demonstrate that our mathematical model provides a quantitative principle to simulate the direction of glucose flux at both subcellular and population levels in human cancer cells. Lastly, we demonstrate to predict 2-deoxyglucose-mediated alteration of glucose flux in a population level based on subcellular high-content imaging data. This is joint work with Miji Jeon and Songon An (Department of Chemistry and Biochemistry, UMBC).