CPT1A: the future of heart disease detection and personalized medicine?

Abstract

Fatty acid oxidation in the mitochondria is essential for energy homeostasis in the absence of a consistent energy supply, such as in prolonged fasting or exercise. Long-chain fatty acids, which make up the major dietary fraction of fatty acids, cannot enter the mitochondria by simple diffusion.1 The carnitine palmitoyltransferase (CPT) system is a mitochondrial enzymatic complex which acts to transport long chain fatty acids across the outer and inner mitochondrial membrane.2 The system is made up of two distinct proteins corresponding to the outer and inner membrane forms: carnitine palmitoyltransferase 1 (CPT1) and 2 (CPT2), respectively. CPT2 is ubiquitously expressed, while CPT1 exists in three tissue-specific forms, namely CPT1A in the liver, CPT1B in the muscle, and CPT1C in the brain.3 The function of CPT1 is best understood in the liver, where CPT1A controls the fatty acid flux through the esterification and oxidative pathways with its sensitivity to malonyl-CoA, a potent CPT1 inhibitor which acts as an important intermediate in fatty acid biosynthesis. During fasting, malonyl-CoA inhibition of CPT1A is halted so that long chain fatty acid oxidation and subsequently ketogenesis become enhanced. In the postprandial state, the concentration of malonyl-CoA increases, CPT1A inhibition ensues, and long chain fatty acids are directed toward esterification. The regulation of CPT1 in extra-hepatic tissues is less clear, however, it is known to be an important constituent of energy homeostasis and maintenance in heart and skeletal muscle as well.1