Carnitine palmitoyltransferase 1-alpha (CPT1A)

Carnitine palmitoyltransferase 1-alpha (CPT1A) is a critical rate-limiting enzyme located on the outer mitochondrial membrane that facilitates the entry of long-chain fatty acids into the mitochondria for beta-oxidation [1, 8]. It catalyzes the conversion of long-chain acyl-CoAs into acylcarnitines, which is essential for maintaining energy homeostasis during periods of fasting or increased metabolic demand [3, 12]. Primarily expressed in the liver, kidney, and brain, CPT1A is endogenously inhibited by malonyl-CoA, linking fatty acid synthesis and oxidation pathways [1, 6]. In clinical research, CPT1A is frequently overexpressed in various malignancies, such as prostate, breast, and gastric cancers, where it supports the high energetic requirements and survival of tumor cells under metabolic stress [2, 9, 13]. Pharmacological inhibition of CPT1A using agents like Etomoxir or Teglicar has been explored as a strategy to disrupt cancer metabolism and treat metabolic disorders like type 2 diabetes [5, 12]. However, targeting CPT1A presents significant safety challenges, including risks of hepatotoxicity, hypoketotic hypoglycemia, and potential cardiac effects if isoform specificity is not maintained [3, 10].

Other names

CPT1CPTI-LL-CPT1Carnitine palmitoyltransferase ICarnitine palmitoyltransferase 1ACarnitine O-palmitoyltransferase 1, liver isoform

Inhibition of carnitine palmitoyltransferase 1-alpha activity to block the conversion of long-chain acyl-CoA and carnitine into acylcarnitine, thereby preventing the transport of fatty acids into the mitochondria and reducing fatty acid beta-oxidation.