Mammalian cells in culture produce large amounts of lactate.  However, under certain culture conditions metabolic shift to lactate consumption has been observed which is associated with better productivity. Such shift is elusive in nature where under similar conditions some cells metabolically shift whereas others continue to produce lactate.  To examine this behavior we employed a mechanistic kinetic model for central metabolism. Allosteric regulations of glycolytic enzymes give rise to multiplicity of states in glycolytic activity and the steady state topology is affected by glucose, lactate and growth rate. The switch from the lactate production to consumption occurs only at certain region in the steady state topology. This analysis enabled us to identify the culture conditions that induce metabolic shift. Insights from such an analysis reveal new ways of inducing robust metabolic shift through use of metabolic engineering approaches for achieving higher productivities.

Metabolic shifts to lactate consumption: Deciphering the underlying mechanisms and key triggers

245th National Meeting (2013)

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