A kinetic modelling approach to study the role of energy regulatory pathways in CHO cells

A kinetic metabolic model for Chinese hamster ovary (CHO) cells primary metabolism is presented. The model considers the catabolism of the main nutrients (glucose and glutamine), including glycolysis, pentose phosphate pathway, TCA cycle and respiratory chain. The model describes growth kinetics as a function of the major precursors for biomass synthesis (lipids, sugar phosphates, nucleic acids and amino acids). The fuelling cycles are also described and used in metabolic fluxes regulation. Fluxes kinetics are described by Michaelis-Menten type equations, considering the metabolites, energy shuttles (ATP/ADP) and other cofactors (NAD/H and NADP/H). Moreover, pathway regulation is modeled using sigmoid switch functions in order to avoid on/off step behavior. This model framework was recently used successfully to simulate plant cell cultures. In the present work, we present the model calibration results using previous recombinant t-PA CHO cells cultures in bioreactor. The model showed to describe cell energetic state as well as cell behavior with culture time.