TABLE 10.

Key points connection between this and carbon dioxide (CO₂).

Key point	Description
Glycolytic Metabolism and Carbon Dioxide Production	The predominant glycolytic metabolism in tumor cells significantly reduces mitochondrial activity, leading to a decrease in CO₂ production. Under normal aerobic conditions, cells metabolize glucose through the tricarboxylic acid (TCA) cycle in the mitochondria, producing CO₂ as a byproduct. However, in tumor cells, glucose is primarily converted to pyruvate and then reduced to lactic acid, bypassing the TCA cycle and thereby reducing CO₂ generation
Presence of Lactic Acid in the Extracellular Environment	The lactic acid produced by tumor cells is excreted into the extracellular environment, where it dissociates into lactate and hydrogen ions (H⁺). This dissociation contributes to the acidification of the tumor microenvironment, creating weakly acidic conditions. In healthy tissues, the buffering of lactic acid can release CO₂, which then diffuses into red blood cells and enhances the Bohr effect, facilitating the release of oxygen from hemoglobin
Acidic pH and Intracellular Oxygen Levels	In the tumor microenvironment, however, the lack of significant CO₂ production means that this buffering process does not generate CO₂ to enhance the Bohr effect. Consequently, the mildly acidic pH of the tumor microenvironment impairs the release of oxygen from hemoglobin, as there is no sufficient CO₂ to shift the oxygen dissociation curve. This impairs the diffusion gradient necessary for oxygen to efficiently enter tumor cells, leading to intracellular hypoxia. This decreases the release of oxygen from hemoglobin, contributing to intracellular hypoxia by impairing the diffusion gradient necessary for oxygen to efficiently enter tumor cells. This hypoxic condition sustains the reliance on anaerobic glycolysis, perpetuating the cycle of lactic acid production and extracellular acidification