Figure 1.

A schematic representation of fatty acid (FA) metabolism. Long chain FAs, such as palmitic acid, are actively transported across the cell membrane by membrane-bound transporters, such as CD36 and FA transport protein (FATP). FA binding proteins (FABPpm, membrane-associated; FATP, cytosolic) facilitate the transfer. In the cytosol, FAs can either be stored in lipid droplets or undergo enzymatic conversion to FA-acyl-CoA that can enter the mitochondria via the carnitine palmitoyltransferases 1 and 2 (CPT1, CPT2) transporters, located on the outer and inner mitochondrial membranes, respectively. The activation of CPT1 is a survival signal and inhibits the oligomerisation of the pro-apoptotic Bcl-2 family proteins, Bak, and Bax. Inside mitochondria, FA-acyl-CoA molecules are broken down in a series of enzymatic reactions known as ß-oxidation. FADH₂ and NADH are released and are used as co-factors in the electron transport chain (ETC) to produce ATP. Acetyl-CoA is released and enters the tricarboxylic acid cycle (TCA), where it is oxidised for citrate production. Citrate is transported to the cytosol where it is converted to acetyl-CoA. Acetyl-CoA carboxylase 1 (ACC1) –mediated conversion of acetyl-coA to malonyl-CoA is the rate-limiting step in fatty acid synthesis. Malonyl-CoA in particular when produced by ACC2, inhibits CPT1 and thus limits ß-oxidation.