Year: 2015
Type: article
Abstract: Tumors with high glycolytic or hypoxic properties must produce sufficient levels of acetyl-CoA to maintain cellular survival and proliferation under adverse nutrient conditions. Acetyl-CoA can be generated by oxidation of glucose, glutamine, or fatty acids. There are principal differences between the metabolism of normal, well-fed cells and tumor cells, especially under nutrient-deprived conditions. Whereas the former consume glucose/pyruvate/acetyl-CoA-derived citrate to synthesize acetyl-CoA, which is then used for fatty acid and cholesterol synthesis, generation of nucleotides and amino acids, and histone acetylation, the latter divert the main metabolite of glucose into aerobic glycolysis from pyruvate-derived mitochondrial acetyl-CoA to lactate. The “bioenergetic substrate gap” develops when under oxygen-limiting conditions the ability of a cell to make acetyl-CoA is impaired, and the question arises how sufficient amounts of citrate via ATP citrate lyase are produced. In the brain, glial cells are capable of oxidizing acetate.
Source: Neuro-Oncology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4248895435