Glutamine, Glutaminolysis, Metformin & Aspartate in Cancer

The entry of acitate and betahydroxybutyrate into the Krebs cycle varies in different cells, as each has different ketolytic enzymes allowing different entry points. The Krebs cycle is not as straightforward as previously thought, especially in cancer cells, with various pathways like the malate aspartate shuttle being associated with cancer cells. Recent research in nature suggests that aspartate may be a rate-limiting step in cancer metabolism in the mitacondria, and metformin may exert anti-cancer benefits by interfering with aspartate degradation. Glutamine serves as a fermentable fuel, while ketones are non-fermentable, and cancer cells primarily use glucose and glutamine as fermentable fuels. Glutaminolysis, driven by the malate aspartate shuttle, is a major focus for cancer researchers, although targeting glutamine poses challenges due to potential severe side effects.