Model-based analysis of cellular metabolism can facilitate our understanding
of intracellular kinetics and aid the improvement of
cell growth and biological product manufacturing. In this thesis,
a model-based kinetic study of cytosolic glucose metabolism is presented.
Based on the Kyoto Encyclopedia of Genes and Genomes and
the Braunschweig Enzyme Database, a metabolic map of cytosolic
glucose metabolism including 30 metabolites and 36 reactions, which
consists of glycolysis, glucogenesis, pentose-phosphate pathway and
adjacent metabolic reactions, has been constructed. Kinetic modelling
was performed according to this metabolic map and reported enzyme
kinetic studies, considering regulation and/or inhibition by products,
substrates or other metabolites. Parameters were estimated based on
previous parameter information and metabolic flux analysis studies, as
well as results from our own experiments. Simulation results for cell
population kinetics, metabolite concentrations and reaction rates have
shown good agreement with experimental data. Furthermore, in silico
case studies including global sensitivity analysis, feeding lactate as
a co-substrate and the regulation effect by fructose 2,6-bisphosphate
were performed in order to find strategies to increase metabolic efficiency
in Chinese hamster ovary cells in an attempt to provide a guide
for process optimisation. In conclusion, our model provides a deep
look into cytosolic glucose metabolism and the simulation results have
suggested a suitable direction to increase the metabolic efficiency.