Fatty acid oxidation metabolism overview

Figure illustrating the carnitine cycle. The mitochondrial membrane is not permeable to long-chain fatty acids; a multistep process is therefore required for these compounds to be used by mitochondria. In the muscle cytoplasm, long-chain fatty acids are first activated by long-chain acyl-CoA synthetase (ACS) to their CoA thioesters. The CoA thioesters are subsequently linked with carnitine by the enzyme carnitine palmitoyltransferase 1 (CPT 1) located on the inner side of the outer mitochondrial membrane. The acylcarnitine form of the long-chain fatty acid, palmitoylcarnitine, is then transferred across the inner mitochondrial membrane by carnitine:acylcarnitine translocase. Once in the mitochondrial matrix, it is converted back to free acyl-CoA derivative and carnitine by carnitine palmitoyltransferase 2 (CPT 2) on the inner side of the inner mitochondrial membrane. Once carnitine is released, the long-chain acyl-CoA derivative enters the beta-oxidation pathway. With every complete cycle, a two-carbon fragment is cleaved, and an acetyl-CoA molecule is released.