Question

Does diet or host metabolism play a role in acetate metabolism in tumors or acetate dependent tissues?

Answer 1

Acetate and Acetate related metabolic products like Acetyl-CoA performs numerous functions in metabolism. It includes lipid biosynthesis, energy production etc. Acetate is derived from the glycolysis i.e., as an end product of pyruvate.

Acetyl CoA synthetases catalyse the conversion of Acetate into Acetyl-CoA has shown its role in various types of cancer including hepatocellular carcinoma, breast cancer etc. This indicates that Acetate plays its role in providing the nutritional source for cancer. There are some reasons how acetate (metabolic product) can help in the progression of tumour cells or cancer:

1. Acetate plays a role as nutritional source in tumours via its bioenergetics pathways.
2. Even when in low concentrations, the acetate may still be present and can be obtained via inter and intracellular recycling of its molecules.
3. In response to the nutritional stress conditions, the acetyl-CoA synthetase is utilized which develops in different types of cancer.
4. Acetate can also be produced in the microenvironmental conditions. In hydrolysis conditions, Acetyl CoA hydrolase generates Acetate which contributes to the acetate sources in tumour cells.
5. During hypoxic conditions, the lipid biosynthesis occurs at a greater pace forming its more contribution in Acetate production that contributes to the local microenvironment and confers its role in tumour cells.
6. Another important factor in this regard could be mTORC2, it is an important protein complex which performs its function by regulating cell proliferation and metabolism of the cytoskeleton. It is itself regulated by growth factors, insulin and nutrient levels. During cancer or tumour conditions when it is turned on it performs hyperactivity in metabolic functions. This high generated metabolism contributes by allowing cancer cells to take up increase amount of glucose and acetate from the system which provides that extra amount of energy or fuel needed for the uncontrolled growth of tumour cells.