carnitineshuttlen

The standard term for the system is the carnitine shuttle, a biochemical mechanism that enables long-chain fatty acids to enter the mitochondrial matrix for beta-oxidation. The combined form "carnitineshuttlen" is not commonly used in scientific literature. The shuttle consists of carnitine, the outer and inner mitochondrial membrane enzymes CPT1 and CPT2, and the carnitine-acylcarnitine translocase (CACT), and it is essential for efficient fatty acid utilization in energy metabolism.

Mechanism: In the cytosol, fatty acids are activated to acyl-CoA by acyl-CoA synthetase. CPT1 on the outer mitochondrial membrane transfers the acyl group from acyl-CoA to carnitine, forming acylcarnitine. CACT transports acylcarnitine across the inner membrane into the matrix. Inside, CPT2 transfers the acyl group back to CoA, regenerating acyl-CoA for beta-oxidation, while free carnitine is returned to the cytosol. Some tissues also express carnitine acetyltransferase (CrAT), which interconverts acetyl-CoA and acetylcarnitine to balance acetyl groups.

Regulation and significance: CPT1 activity is inhibited by malonyl-CoA, integrating fatty acid oxidation with carbohydrate metabolism. Transcriptional and hormonal signals modulate the expression and activity of CPT1 and related transport proteins, adapting to energy demand. The shuttle is vital in tissues with high fatty acid oxidation needs, such as heart and skeletal muscle; disruption impairs energy production and can lead to metabolic crises during fasting.

Clinical notes: Genetic defects include CPT1 deficiency, CPT2 deficiency, and primary carnitine transporter deficiency (SLC22A5). Clinical presentation ranges from hypoketotic hypoglycemia to muscle weakness and cardiomyopathy. Diagnosis involves metabolic testing and genetic analysis, and management emphasizes preventing fasting, dietary strategies, and, in selected cases, L-carnitine supplementation.