Subverting the textbook: Not glucose! Cancer cells mainly feed on lactic acid
For a long time, lactic acid has been regarded as a waste product produced by metabolism under anaerobic conditions. However, a paper published in the journal Nature makes a subversive point: lactic acid is not only a metabolite under anaerobic conditions, but also may be the most important energy carrier for the human body. At the same time, it is also the most important direct source of nutrition for cancer cells. This research may open up new ideas for the study of diseases such as cancer.
Carbohydrates, proteins, and fats are the three most important nutrients for the human body. In the food we consume every day, these three nutrients are decomposed, absorbed, and converted by the digestive system. They exist in the blood in the form of glucose, amino acids, and ketone bodies, and are further absorbed and utilized by tissue cells.
Metabolism under aerobic and anaerobic conditions
Under aerobic conditions , the chemical reaction in which these three nutrients release all their energy as the fuel of life is called the tricarboxylic acid cycle (TCA). This chemical reaction is not only an important step in aerobic oxidation, but also the hub of carbohydrate, protein and fat metabolism. The three nutrients undergo a series of biochemical reactions, eventually entering the tricarboxylic acid cycle in the form of pyruvate, which eventually produces energy and carbon dioxide.
In the absence of oxygen, the situation is different . Biology textbooks tell us that glucose can only be partially oxidized, releasing a small amount of energy to produce lactic acid. Lactic acid has long been seen as a product of insufficient oxidation of glucose, and elevated levels of lactic acid in the blood usually mean that tissues are deprived of oxygen.
The new role of lactic acid
Now, a new study challenges this common sense: lactic acid is not just a metabolite in anaerobic conditions, it may well play a more important and poorly understood role in the entire vast energy metabolism.
More important energy carrier
A new study published in the journal Nature has found that lactate is not just a metabolite in the absence of oxygen. It is a key energy carrier like glucose, amino acids, and ketone bodies, even more important than previously thought.
Researchers from Rutgers Cancer Institute and Princeton University systematically measured the levels of different metabolic intermediates in the blood circulation of mice to measure their proportion in the energy supply. Using the C isotope labeling method, they tracked the circulation of more than a dozen carbon-containing metabolic intermediates, including lactic acid, glucose, and various amino acids. According to previous studies, the largest carbon-containing compound in circulation should be glucose, but the researchers found that lactic acid actually topped the list with 2.5 times the blood flux of glucose, which is 5 times more than pyruvate, glycerol (one of the products of lipolysis), and several amino acids.
The discovery of rewriting textbooks
Previous biochemical knowledge tells us that muscle tissue produces lactic acid when it is deprived of oxygen, which then enters the bloodstream and is converted to glucose in the liver through gluconeogenesis.
However, according to the latest results of this study, researchers have found that lactic acid can be used as an important energy substance for transfer within and between tissues. Even the main way for glucose to enter the tricarboxylic acid cycle is to be converted into lactic acid first. This suggests that lactic acid may play a more important role in the entire energy metabolism process of organisms. This provides new ideas for future research on diabetes and other energy metabolism-related diseases. The significance of blood lactate level detection may also need to be reassessed clinically.
