Tumor Cells are Vitally Dependent upon Ketolysis, Inhibition of Succinyl CoA: 3-Oxoacid-CoA Transferase Should Block Them

In tumor cells, ketolysis becomes the unique source of mitochondrial acetyl CoA. Indeed, the glycolytic acetyl CoA production is blocked (pyruvate kinase and pyruvate dehydrogenase are inhibited by phosphorylation). Whereas, the fatty acid degradation into acetyl CoA is also turned off by malonyl CoA, the product of acetyl CoA carboxylase, which forms with the synthesis of fatty acids, to automatically close down their degradation, by inhibiting the fatty acid mitochondrial transporter. Thus, inhibiting the ketolytic supply of acetyl CoA and the specific ketolytic enzyme: succinyl-CoA: 3-oxoacid-CoA transferase, should block the tumor. However, tumor cells are able to take-up acetate and convert it into acetyl CoA in their cytosol via an acetyl CoA synthetase and inhibiting this enzyme would make it difficult for tumor cells to survive.