Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) (CPT1A)

Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) is a critical regulatory enzyme located on the outer mitochondrial membrane that serves as the rate-limiting step in the mitochondrial beta-oxidation of long-chain fatty acids [1, 2, 6]. It catalyzes the transfer of acyl groups from long-chain fatty acyl-CoA to carnitine, forming acylcarnitines that are subsequently transported into the mitochondrial matrix for energy production [1, 6, 8]. CPT1A is primarily expressed in the liver, kidney, and brain, and its activity is physiologically inhibited by malonyl-CoA, a key intermediate of fatty acid synthesis [2, 8, 12]. In metabolic disorders such as type 2 diabetes and obesity, pharmacological inhibition of CPT1A is explored to reduce excessive fatty acid oxidation and promote a metabolic shift toward glucose utilization, which can improve insulin sensitivity [1, 4, 8]. Furthermore, CPT1A is frequently overexpressed in various malignancies, including breast and ovarian cancers, where it supports tumor cell survival, proliferation, and metabolic flexibility [2, 5, 17, 20]. While inhibitors like etomoxir have demonstrated therapeutic potential in preclinical studies, their clinical development has been hindered by safety concerns such as severe hypoglycemia and hepatotoxicity [2, 7, 13].

Other names

Carnitine palmitoyltransferase 1ACPT1-LCPT1L-CPT1Succinyltransferase CPT1A

CPT1A inhibitors bind to the enzyme on the outer mitochondrial membrane, preventing the conversion of long-chain fatty acyl-CoA to acylcarnitine [1, 4]. This blockade restricts the entry of long-chain fatty acids into the mitochondria, thereby reducing fatty acid beta-oxidation and shifting cellular energy production toward glucose metabolism [1, 2, 4].