Carnitine palmitoyltransferase system and related carnitine shuttle enzymes (CPT system)

The carnitine palmitoyltransferase (CPT) system, also known as the carnitine shuttle, is a critical metabolic pathway responsible for the transport of long-chain fatty acids across the mitochondrial membranes for beta-oxidation. This system comprises three primary components: carnitine palmitoyltransferase 1 (CPT1), located on the outer mitochondrial membrane; carnitine-acylcarnitine translocase (CACT), which facilitates the exchange of acylcarnitines and free carnitine across the inner membrane; and carnitine palmitoyltransferase 2 (CPT2), situated on the inner mitochondrial membrane. CPT1 is the rate-limiting enzyme of this process and exists in three tissue-specific isoforms (CPT1A, CPT1B, and CPT1C), which are allosterically inhibited by malonyl-CoA. Dysregulation of this system is implicated in various diseases, including heart failure, where shifting metabolism from fatty acids to glucose can be beneficial, and cancer, where many tumors rely on fatty acid oxidation for survival and proliferation. Pharmacological modulation includes CPT1 inhibitors like etomoxir and perhexiline, which have been explored for cardiovascular and oncological indications, though safety concerns such as hepatotoxicity and peripheral neuropathy have limited their clinical use.

Other names

Carnitine shuttle systemCPT systemFatty acid transport systemCarnitine acyltransferase system

Inhibition of CPT1 or CPT2 to reduce fatty acid oxidation and promote glucose utilization; activation of CPT1 to enhance fat burning; carnitine supplementation to restore shuttle function in deficiency states.