The dynamics in glycolysis activity is affected by the isozyme composition and their relative expression FTY720 levels in the cell. Different cell lines express glycolysis enzymes at somewhat different levels that might affect their metabolic behavior. This may be part of the reason that the propensity to switch to a low flux or lactate consumption state differs among different cell lines. But even for the same cell line, under presumably ��identical�� culture conditions, the switch from a high flux state to a low flux state is not robust as shown in the compiled historical data. We demonstrated that one possible explanation for this is the subtle difference in the glucose addition time. The complex topology of flux response to glucose and lactate concentration makes the precise control of shift down to low flux state unpredictable. Various studies have been undertaken to explore the means of facilitating metabolic shift to a low flux state and lactate consumption metabolic state. In this study, we demonstrated that one can direct cell LEE011 metabolism to a low flux state through control of glucose level at lower concentration range. Upon successful metabolic shift, even if the glucose level is reset to a higher level, the flux will remain at a low flux state. The experimental data presented in this study provide further evidence to support our model prediction. Others have reported that the switch in the metabolism only happens in cell lines which maintain higher oxidative capacity in the late stages of the cultures. Transcriptome data of recombinant mouse myeloma indicate that the oxidative phosphorylation genes are up-regulated at transcript level under lactate consumption conditions. Supplementation of copper has been reported to enhance the lactate consumption phenotype in late stages of fed-batch cultures. Through transcriptome analysis on copper-supplemented culture, the early growth response protein 1, a gene also related to negative regulation of AKT through PTEN, was shown to be up-regulated in high copper condition. Alternatively, in a separate study, the expression of anti-apoptotic genes E1B-19K and Aven was shown to favor lactate consumption. Recently, there has been increasing interest in employing continuous culture or continuous culture with cell recycle for cell cultivation. The rationale is that continuous processes minimize equipment down time and increase overall productivity. Since multiplicity of metabolic state occurs under some conditions, it is likely that those distinctive metabolic states will also lead to different steady states of the culture: at a high flux state, the vast majority of glucose is converted to lactate resulting in a low viable cell concentration at the steady state reached; conversely at a low flux state, little glucose is diverted to lactate, and a high cell concentration is achieved.