title: Glycolysis is governed by growth regime and simple enzyme regulation in adherent MDCK cells.
abstract: Due to its vital importance in the supply of cellular pathways with energy and precursors, glycolysis has been studied for several decades regarding its capacity and regulation. For a systems-level understanding of the Madin-Darby canine kidney (MDCK) cell metabolism, we couple a segregated cell growth model published earlier with a structured model of glycolysis, which is based on relatively simple kinetics for enzymatic reactions of glycolysis, to explain the pathway dynamics under various cultivation conditions. The structured model takes into account in vitro enzyme activities, and links glycolysis with pentose phosphate pathway and glycogenesis. Using a single parameterization, metabolite pool dynamics during cell cultivation, glucose limitation and glucose pulse experiments can be consistently reproduced by considering the cultivation history of the cells. Growth phase-dependent glucose uptake together with cell-specific volume changes generate high intracellular metabolite pools and flux rates to satisfy the cellular demand during growth. Under glucose limitation, the coordinated control of glycolytic enzymes re-adjusts the glycolytic flux to prevent the depletion of glycolytic intermediates. Finally, the model's predictive power supports the design of more efficient bioprocesses.
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Rehberg
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
authors.forename: Joachim B
authors.initials: JB
authors.lastname: Ritter
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany; Otto von Guericke University Magdeburg, Chair of Bioprocess Engineering, Magdeburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Reichl
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D003198:Computer Simulation; D003470:Culture Media; D004285:Dogs; D004798:Enzymes / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D053858:Metabolic Networks and Pathways; D008954:Models, Biological
chemical_list: D003470:Culture Media; D004798:Enzymes