oxidationCPT1B

CPT1B, or carnitine palmitoyltransferase 1B, is the muscle isoform of the enzyme carnitine palmitoyltransferase 1. It is a mitochondrial outer membrane enzyme that initiates mitochondrial long-chain fatty acid oxidation in skeletal muscle and is encoded by the CPT1B gene. This isoform is expressed predominantly in skeletal muscle tissue, with other CPT1 family members present in liver (CPT1A) and brain (CPT1C).

Functionally, CPT1B catalyzes the formation of acyl-carnitine from long-chain acyl-CoA and L-carnitine, representing the rate-limiting step in mitochondrial beta-oxidation. This reaction enables long-chain fatty acids to cross the outer mitochondrial membrane; once in the matrix, the acyl-carnitine is shuttled by carnitine palmitoyltransferase 2 (CPT2) and the carnitine shuttle to revert to acyl-CoA for oxidation.

Regulation of CPT1B ties fatty acid oxidation to the cellular energy state. Malonyl-CoA inhibits CPT1B, linking FAO flux to biosynthetic and energy status. Metabolic signals such as AMP-activated protein kinase (AMPK) activity, fasting, and hormonal cues influence malonyl-CoA levels, thereby modulating CPT1B activity. During fasting or exercise, reduced malonyl-CoA promotes greater fatty acid oxidation via increased CPT1B activity.

Clinical notes indicate that rare variants in CPT1B have been described in association with skeletal muscle metabolic myopathy and exercise intolerance, including episodic rhabdomyolysis in some cases. Diagnosis typically involves genetic testing and assessment of fatty acid oxidation capacity in muscle. Treatment strategies focus on dietary management to optimize energy substrate availability and to avoid prolonged fasting, with management tailored to the individual.