Lactic acid is an inevitable metabolic byproduct during cell culture, and its accumulation is not desirable because it can affect cell growth, protein production, and quality. This article provides a brief overview of the reasons why lactic acid affects cell growth and how to reduce its cytotoxicity.

In the early stage of CHO cell culture, there is often a small accumulation of lactate, especially during the logarithmic growth phase when cell metabolism is vigorous. Generally, cells can consume this lactate metabolism. But sometimes this is not smooth for certain cell lines, and the accumulation of lactic acid is fatal to the cells. Lactic acid mainly comes from glucosefullyOxidation and the accumulation of lactic acid can lower the pH of the system. Adding alkaline solution to raise the pH often increases the osmotic pressure of the system, thereby affecting the normal growth and metabolism of cells. If pH is not adjusted with alkaline solution, a low pH environment is not good news for enzymes in the cell body. The decrease in enzyme activity will limit cell metabolism and affect cell growth.

To alleviate the effects of lactic acid on cell growth and protein production, it is possible to construct cell lines with high tolerance to environmental stress, or optimize cell culture strategies. Replacing glucose with slowly metabolized sugars as a carbon source can reduce the accumulation of lactic acid, such as the use of galactose, fucose, and maltose.

When lactate accumulates to a certain extent, the metabolic pathway of cells can be altered by the concentration of glucose, converting glucose metabolism into lactate metabolism, thereby reducing lactate accumulation. However, the impact of low sugar consumption strategies on protein quality is not clear. Genetic modification of cells can also reduce lactate accumulation, such as deleting the lactate dehydrogenase (LDH) gene and amplifying the pyruvate carboxylase (PYC2) gene. LDH is an important enzyme that catalyzes the conversion of pyruvate to lactate, while PYC2 is a catalytic enzyme involved in the conversion of lactate, pyruvate, amino acids, and glycerol to glucose. Genetic modification of both can reduce lactate accumulation in metabolic pathways.

Although the above methods can reduce lactate accumulation, their operability is not strong. I think copper ions（The addition of Cu2+is currently the best method to reduce lactate accumulation. In addition to its inhibitory effect on lactate accumulation, many studies have mentioned that Cu2+promotes cell growth.
So, if you need real-time monitoring of glucose and lactate levels,M ü ller, GermanyGlucose lactate analyzerIt's a good choice for you.