Carnitinedependent

Carnitinedependent, or carnitine-dependent, describes biochemical processes that require carnitine to function, most notably the mitochondrial transport of long-chain fatty acids for beta-oxidation. In humans, the carnitine shuttle consists of carnitine palmitoyltransferase I (CPT I) on the outer mitochondrial membrane that converts acyl-CoA to acylcarnitine, the carnitine-acylcarnitine translocase (CACT) that shuttles acylcarnitine across the inner membrane, and carnitine palmitoyltransferase II (CPT II) that regenerates acyl-CoA inside the matrix. This pathway is essential for the efficient oxidation of long-chain fatty acids and is thus referred to as carnitine-dependent.

Long-chain fatty acids rely on this shuttle for entry into the mitochondrion, whereas short- and medium-chain fatty acids can cross the mitochondrial membranes independently of the shuttle. Beyond transport, carnitine participates in the transient detoxification of acyl groups by forming acylcarnitines, which can be transported in the bloodstream and metabolized or excreted as needed.

Clinically, defects affecting the carnitine shuttle or transporter cause carnitine-dependent fatty acid oxidation disorders. These include deficiencies of CPT I, CPT II, or CACT, and primary carnitine deficiency due to mutations in the SLC22A5 transporter. Presentations vary but can include hypoketotic hypoglycemia, muscle weakness, cardiomyopathy, and periodic metabolic crises. Secondary deficiencies may occur with other metabolic diseases or certain medications.

Carnitine is obtained from diet (notably red meat and dairy) and is synthesized endogenously from lysine and methionine in liver and kidney. Cellular uptake is mediated by transporters such as OCTN2 (SLC22A5). Management of carnitine-dependent disorders emphasizes avoiding fasting, maintaining adequate carbohydrate intake, and, in some cases, L-carnitine supplementation.