How is lactate metabolized?
The lactate diffuses out of the cells and is converted to pyruvate and then is aerobically metabolized to carbon dioxide and ATP. The heart, liver, and kidneys use lactate in this manner. Alternatively, hepatic and renal tissues can use lactate to produce glucose via another pathway referred to as gluconeogenesis.
How is lactate produced in cell culture?
Lactate is one of the key waste metabolites of mammalian cell culture. High lactate levels are caused by high aerobic glycolysis, also known as the Warburg effect, and are usually associated with adverse culture performance.
Why do cells consume lactate?
► Lactate consumption in cell culture correlates to enhanced product yields. ► Occurs during slow growth and under low glycolytic flux and high lactate level. ► High lactate levels inhibit PFK activity thereby repress glycolysis flux.
Do cells consume lactate?
Typically lactate is strongly produced during the exponential growth phase, while its net consumption is frequently observed when cells enter into the stationary phase. Such a metabolic shift is desirable because it seems to favor optimal process performance.
What is lactic acid metabolism?
The Cori cycle (also known as the lactic acid cycle), named after its discoverers, Carl Ferdinand Cori and Gerty Cori, is a metabolic pathway in which lactate produced by anaerobic glycolysis in muscles is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized …
How does lactate cause metabolic acidosis?
Lactic acidosis occurs when lactic acid production exceeds lactic acid clearance. The increase in lactate production is usually caused by impaired tissue oxygenation, either from decreased oxygen delivery or a defect in mitochondrial oxygen utilization.
How do you reduce lactate production in cell culture?
Control of glucose at low levels in the culture medium—so as to limit the supply of glucose to the cells—has been employed for over three decades to reduce lactic acid production (Table 1). This can be achieved through various means, such as direct measurement and automatic or manual feedback control of glucose levels.
What is the fate of lactate in mammalian cells?
When lactate is used as an energy source, lactate carbon is ultimately inserted into the tricarboxylic acid (TCA) cycle in the mitochondria. It is generally assumed that lactate is first oxidized to pyruvate in the cytosol prior to entering the mitochondria1,6.
Why does lactate inhibit glycolysis?
Furthermore, in mamma- lian muscle, lactate not only alters the intracellular concentra- tions of F6P and F1,6BP but also modulates 6-phosphofructo- 1-kinase (PFK), the major enzyme regulating glycolysis (22), dissociating the enzyme tetramers into dimers, and therefore inhibiting it (6).
How does lactate affect cell growth?
Lactate has been reported to inhibit cell growth and cell metabolism, and to decrease productivity, partially due to the changes in medium osmolarity, in hybridoma [23] and in Chinese hamster ovary (CHO) cells [15].
Is lactate the same as lactic acid?
The technical difference between lactate and lactic acid is chemical. Lactate is lactic acid, missing one proton. To be an acid, a substance must be able to donate a hydrogen ion; when lactic acid donates its proton, it becomes its conjugate base, or lactate.