At the beginning of cell culture and in the log phase, despite the considerable need for energy and ATP, cells deliberately convert glucose to lactate, and the amount of lactate usually increases. Then in the stationary phase, lactate shift happens and cell start to consume lactate. What could be the reason for this cell behavior?
Why does the cells not consume glucose completely from the beginning?
Thank you in advance for you time?
Hello Mehdi Amiri Goushki
Glucose is a major energy source for mammalian cells grown in culture. Most of the glucose consumed by mammalian cells cultivated in vitro is converted to lactate. Although conditions are aerobic, in most cases, glucose is not completely oxidized. Depending on the culture conditions and the cell type, about 50-100% of glucose is converted to lactate.
Lactate is one of the key waste metabolites of mammalian cell culture and is usually associated with adverse culture performance. Therefore, reducing lactate accumulation has been an ongoing challenge in cell culture development to improve growth, productivity, and process robustness.
The pyruvate dehydrogenase complex (PDC) plays a crucial role for the fate of pyruvate, as it converts pyruvate to acetyl coenzyme A (acetyl-CoA). The PDC activity can be indirectly increased by inhibiting the PDC inhibitor namely, pyruvate dehydrogenase kinase II.
Pyruvate dehydrogenase kinase II inhibits the pyruvate dehydrogenase complex (PDC) through phosphorylation. When the PDC is phosphorylated, it ceases to function. Therefore, pyruvate dehydrogenase kinase II is a regulatory enzyme that controls the function of the PDC namely, the conversion of pyruvate into acetyl CoA.
So, if PDC inhibitor is inhibited it will result is less pyruvate being made available for lactate formation.
Dichloroacetate (DCA) is one such inhibitor that will help pyruvate dehydrogenase, the rate-limiting enzyme of aerobic glucose oxidation to convert glycolysis-produced pyruvate to acetyl-CoA that enters the mitochondria and is consumed in the process of oxidative phosphorylation (OXPHOS).
Hope this explanation will help!
Best.
- Badges
- Science topic
- Similar topics
- Biological Science
- Microbiology
- Microorganisms
- Bacteria