carnitine

Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine.

In living cells, carnitine is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids (or fats) for the generation of metabolic energy.

Carnitine exists in two stereoisomers: its biologically active form is L-carnitine, while its enantiomer, D-carnitine, is biologically inactive.

Biosynthesis

In animals, carnitine is biosynthesized primarily in the liver and kidneys from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. During growth or pregnancy the requirement of carnitine might exceed its natural production.

Carnitine in fatty acid metabolism

Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so that they can be broken down through β-oxidation to acyl-CoA to obtain usable energy via the citric acid cycle.

In some organisms such as fungi, the acetate is used in the glyoxylate cycle for gluconeogenesis and formation of carbohydrates.

Fatty acids must be activated before binding to the carnitine molecule to form acyl-carnitine. The free fatty acid in the cytosol is attached with a thioester bond to coenzyme A (CoA). This reaction is catalyzed by the enzyme fatty acyl-CoA synthetase and driven to completion by inorganic pyrophosphatase.

The acyl group on CoA can now be transferred to carnitine and the resulting acyl-carnitine transported into the mitochondrial matrix. This occurs via a series of similar steps:

 1. Acyl-CoA is conjugated to carnitine by carnitine acyltransferase I (palmitoyltransferase) located on the outer mitochondrial membrane

 2. Acyl-carnitine is shuttled inside by a carnitine-acylcarnitine translocase

 3. Acyl-carnitine is converted to acyl-CoA by carnitine acyltransferase II (palmitoyltransferase) located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol.

Carnitine acyltransferase I undergoes allosteric inhibition as a result of malonyl-CoA, an intermediate in fatty acid biosynthesis, in order to prevent futile cycling between fatty acid β-oxidation and fatty acid synthesis.

Pathology

 primary carnitine deficiency
 carnitine palmitoyltransferase I deficiency
 carnitine palmitoyltransferase II deficiency
 carnitine-acylcarnitine translocase deficiency

See also

 carnitine shuttle