Flux balance analysis of CHO cells before and after a metabolic switch from lactate production to consumption

TLDR

Mammalian cell cultures typically consume large amounts of glucose and produce large amounts of lactate, but can switch to a more energy‑efficient state where lactate is consumed. Using a mouse genome‑scale model, the authors performed flux balance analysis of CHO cells before and after a switch from lactate production (with glucose) to lactate consumption (after glucose depletion), and the resulting narrow flux ranges allowed investigation of metabolic changes across the switch. Fluxes through the lower TCA cycle were similar (~60 µmol gDW⁻¹ h⁻¹) in both phases, yet lactate‑consuming cells exhibited an energy efficiency six times higher than lactate‑producing cells. Published in Biotechnol.

Abstract

Abstract Mammalian cell cultures typically exhibit an energy inefficient phenotype characterized by the consumption of large quantities of glucose and the concomitant production of large quantities of lactate. Under certain conditions, mammalian cells can switch to a more energy efficient state during which lactate is consumed. Using a metabolic model derived from a mouse genome scale model we performed flux balance analysis of Chinese hamster ovary cells before and after a metabolic switch from lactate production (in the presence of glucose) to lactate consumption (after glucose depletion). Despite a residual degree of freedom after accounting for measurements, the calculated flux ranges and associated errors were narrow enough to enable investigation of metabolic changes across the metabolic switch. Surprisingly, the fluxes through the lower part of the TCA cycle from oxoglutarate to malate were very similar (around 60 µmol/gDW/h) for both phases. A detailed analysis of the energy metabolism showed that cells consuming lactate have an energy efficiency (total ATP produced per total C‐mol substrate consumed) six times greater than lactate producing cells. Biotechnol. Bioeng. 2013; 110: 660–666. © 2012 Wiley Periodicals, Inc.