Inhibitory Effect of Excessive Glucose on Its Biochemical Pathway and the Growth of Chinese Hamster Ovary (CHO) Cells

GRAPHICAL ABSTRACT

Abstract

In this study, we found the specific growth rate of CHO cells being reduced when glucose increased from 1 to 10 g/L. Under high glucose, we show a 41% increase in lactate dehydrogenase activity consistent with a 70% rate increase in lactate production. The pyruvate kinase activity was significantly increased. However, the activities of citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase involved in the TCA cycle were attenuated. We propose that pyruvate produced from glycolysis is utilized in a lesser extent over the TCA cycle under high-glucose conditions. Thus, the pyruvate is largely converted to lactate, which is toxic to the cells.

Keywords:

• CHO cells
• Growth rate
• Glucose flux in glycolysis
• Glucose and TCA cycle enzymes
• ICDH

ACKNOWLEDGMENTS

We are grateful for Dr. S. J. T. Mao's critical review of this manuscript. We also thank the Aiming for the Top University Program of the National Chiao Tung University and Ministry of Education, Taiwan, ROC, for the support of this study.