Carnitine palmitoyltransferase 1A (CPT1A)

Carnitine palmitoyltransferase 1A (CPT1A) is a rate-limiting enzyme embedded in the mitochondrial outer membrane, primarily found in the liver, that catalyzes the transfer of long-chain fatty acyl groups from CoA to carnitine, forming acyl-carnitines that can be transported across the mitochondrial inner membrane for subsequent β-oxidation in the matrix[1][2][5]. CPT1A is crucial for energy production, especially during fasting or metabolic stress, and malfunctions of this enzyme are linked to severe inherited metabolic diseases and hypoketotic hypoglycemia[5][7]. It also plays an emerging role in cancer cell survival, proliferation, immune evasion, and drug resistance by regulating fatty acid oxidation and ferroptosis resistance, making it an attractive therapeutic target, especially in cancers like acute myeloid leukemia and certain solid tumors[2][4][6][8]. Small molecule inhibitors—such as etomoxir—have been studied for both metabolic diseases and cancer, but off-target effects and lack of isoform selectivity remain challenges for drug development[2][8]. CPT1A expression and activity serve as biomarkers for disease and therapeutic selection, although safety concerns exist due to the enzyme's ubiquitous role in energy metabolism[2][5][7][8].

Other names

Carnitine palmitoyltransferase ILiver-type carnitine palmitoyltransferaseCPT IL-CPT1

Inhibition of fatty acid β-oxidation by preventing long-chain fatty acid transport into mitochondria Induction of ferroptosis in cancer stem cells (when inhibited) Modification of energy and redox states in target tissues