Table 2.

Lactate is More Vital Than Pyruvate for Cancer Cells

	Pyruvate (Pyruvic Acid)	Lactate (Lactic Acid)
Contribution to cancer cells’ extracellular acidity	No	Strong contribution
Conversion to acetyl CoA (active acetate) to start the cycle, ketogenesis, or lipogenesis	Directly via the enzyme pyruvate dehydrogenase. This occurs less in hyperglycolytic cancer cells due to consumption of pyruvate to form lactate and mitochondrial damage	None. Lactate must be converted first into pyruvate via LDH enzyme activity. Usually this does not occur in hyperglycolytic cancer cells due to consumption of pyruvate in forming lactate and the mitochondrial defects that impair the Krebs cycle
Fate in hyperglycolytic cancer cells exhibiting the Warburg effect	Formed from glucose then is rapidly converted to lactate (using LDH to produce the Warburg effect)	Formed from pyruvate, then becomes extruded outside cancer cells producing acidic microenvironment and does not become pyruvate again
Formation and transport	Mainly in normal cells' cytoplasm (from glucose oxidation), then enters the mitochondria using pyruvate translocase enzyme to give acetyl CoA to start the Krebs cycle that needs intact mitochondria and oxygen	In the cytoplasm (from pyruvate resulting from glucose oxidation). Then, lactate goes outside the cells. If lactate enters the mitochondria, it cannot be metabolized further due to mitochondrial lesions. Lactate formation is enhanced by mitochondrial lesions, and absent oxygen (in normal cells), tumour hypoxia or even in the presence of oxygen in cancer cells
Functions in hyperglycolytic cancer cells	Is converted to lactate If there is significant mitochondrial damage, pyruvate cannot start the Krebs cycle or mitochondrial pathways for energy formation (as ketolysis) Helps cancer cells’ migration and metastasis13	Helps cancer cells' metastasis and invasion If there is significant mitochondrial damage, lactate cannot start the Krebs cycle or mitochondrial pathways for energy formation (as ketolysis) Helps cancer cells migration and metastasis13
Causing immunological evasion (escape) of tumours	Never	Very powerful. Lactate inhibits T lymphocytes and suppresses anticancer immunity