Metabolic flux analysis in mammalian cell culture.
Mammalian cell culture metabolism is characterized by glucoglutaminolysis, that is, high glucose and glutamine uptake combined with a high rate of lactate and non-essential amino acid secretion. Stress associated with acid neutralization and ammonia accumulation necessitates complex feeding schemes and limits cell densities achieved in fed-batch culture. Conventional and constraint-based metabolic flux analysis has been successfully used to study the metabolic phenotype of mammalian cells in culture, while (13)C tracer analysis has been used to study small network models and validate assumptions of metabolism. Large-scale (13)C metabolic flux analysis, which is required to improve confidence in the network models and their predictions, remains a major challenge. Advances in both modeling and analytical techniques are bringing this challenge within sight.
Quek
Lake-Ee
LE
Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane QLD 4072, Australia.
Dietmair
Stefanie
S
Krömer
Jens O
JO
Nielsen
Lars K
LK
D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D019149:Bioreactors; D016466:CHO Cells; D002247:Carbon Isotopes; D018929:Cell Culture Techniques / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008322:Mammals / Q000378:metabolism*; D008954:Models, Biological
D000596:Amino Acids; D002247:Carbon Isotopes; D005973:Glutamine; D019344:Lactic Acid; D000641:Ammonia; D005947:Glucose