Effect of pH and glutamine on lactate metabolism in Chinese hamster ovary cell cultures

초록

Chinese hamster ovary (CHO) cells are mainly used for the production of various recombinant proteins. Lactate is accumulated during the cultures and inhibits the metabolism of CHO cells. This causes negative impacts on productivity and protein quality. In this study, we manipulated pH of the medium to control the glucose consumption rate of CHO cells and it can efficiently prevent the production of lactate. At once, we modulated the concentration of glutamine to shift lactate metabolism to lactate consumption. The pH of the medium was adjusted from 6.8 to 7.4 by using hydrogen chloride and sodium hydroxide. Simultaneously glutamine was added at the concentration of 1, 4, and 8 mM. As a result, cell growth was decreased but viability was improved at pH 6.8. Viability was decreased rapidly with high glutamine concentration. At pH 6.8, the rate of glucose consumption was lower than that of pH 7.4 and the production of lactate was reduced. Also, we identified that controlling the concentration of glutamine caused the consumption of lactate rapidly. Overall, controlling of pH and the concentration of glutamine in medium can change lactate metabolism in CHO cells.