Acylcarnitines

Acylcarnitines are esters formed from carnitine and fatty acyl groups. They are key intermediates in the mitochondrial transport of long-chain fatty acids and in the regulation of fatty acid oxidation.

Biochemically, fatty acids are activated to fatty acyl-CoA in the cytosol. The outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (CPT I) converts fatty acyl-CoA to fatty acylcarnitine, which is then shuttled across the inner mitochondrial membrane by carnitine acylcarnitine translocase (CACT). Inside the matrix, carnitine palmitoyltransferase II (CPT II) reconverts the acylcarnitine to fatty acyl-CoA, enabling beta-oxidation. This carnitine shuttle system is essential for the oxidation of long-chain fatty acids.

Acylcarnitines constitute a broad family, including short-, medium-, and long-chain species, as well as hydroxylated and dicarboxylated derivatives. Their levels in biological fluids reflect the activity of beta-oxidation and the capacity of the carnitine shuttle. They can accumulate when there is a block or limitation in fatty acid transport or oxidation, or during metabolic stress.

Clinical relevance is most prominent in fatty acid oxidation disorders. Plasma and urine acylcarnitine profiling, often by tandem mass spectrometry, is used in newborn screening and in diagnosing disorders such as CPT I deficiency, CPT II deficiency, and CACT deficiency. Specific patterns—such as elevated long-chain acylcarnitines or reduced free carnitine—aid interpretation and subsequent management.