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Metabolic Flux Analysis in Systems Biology of Mammalian Cells

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Genomics and Systems Biology of Mammalian Cell Culture

Part of the book series: Advances in Biochemical Engineering Biotechnology ((ABE,volume 127))

Abstract

Reaction rates or metabolic fluxes reflect the integrated phenotype of genome, transcriptome and proteome interactions, including regulation at all levels of the cellular hierarchy. Different methods have been developed in the past to analyse intracellular fluxes. However, compartmentation of mammalian cells, varying utilisation of multiple substrates, reversibility of metabolite uptake and production, unbalanced growth behaviour and adaptation of cells to changing environment during cultivation are just some reasons that make metabolic flux analysis (MFA) in mammalian cell culture more challenging compared to microorganisms. In this article MFA using the metabolite balancing methodology and the advantages and disadvantages of 13C MFA in mammalian cell systems are reviewed. Application examples of MFA in the optimisation of cell culture processes for the production of biopharmaceuticals are presented with a focus on the metabolism of the main industrial workhorse. Another area in which mammalian cell culture plays a key role is in medical and toxicological research. It is shown that MFA can be used to understand pathophysiological mechanisms and can assist in understanding effects of drugs or other compounds on cellular metabolism.

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Acknowledgments

We thank Malina Orsini for valuable help.

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  1. Biochemical Engineering Institute, Saarland University, Campus A 1.5, 66123, Saarbrücken, Germany

    Jens Niklas & Elmar Heinzle

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  1. Jens Niklas
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Correspondence to Elmar Heinzle .

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Editors and Affiliations

  1. , Dept. Chemical Engineering and Material, University of Minnesota, Washington Ave. SE 421, Minneapolis, 55455, Minnesota, USA

    Wei Shou Hu

  2. , Institut für Bioprozess- und Biosystemte, Technische Universität Hamburg-Harburg, Denickestr. 15, Hamburg, 21073, Germany

    An-Ping Zeng

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Niklas, J., Heinzle, E. (2011). Metabolic Flux Analysis in Systems Biology of Mammalian Cells. In: Hu, W., Zeng, AP. (eds) Genomics and Systems Biology of Mammalian Cell Culture. Advances in Biochemical Engineering Biotechnology, vol 127. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2011_99

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