Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids into mitochondria to be oxidized for energy production, and also participates in removing products of metabolism from cells. Given its key metabolic roles, carnitine is concentrated in tissues like skeletal and cardiac muscle that metabolize fatty acids as an energy source. Generally individuals, including strict vegetarians, synthesize enough L-carnitine in vivo.Carnitine exists as one of two stereoisomers (the two enantiomers d-carnitine (S-(+)-) and l-carnitine (R-(−)-)). Both are biologically active, but only l-carnitine naturally occurs in animals, and d-carnitine is toxic as it inhibits the activity of the l-form. At room temperature, pure carnitine is a white powder, and a water-soluble zwitterion with low toxicity. Derived from amino acids, carnitine was first extracted from meat extracts in 1905, leading to its name from Latin, "caro/carnis" or flesh.Some individuals with genetic or medical disorders (such as preterm infants) cannot make enough carnitine, requiring dietary supplementation. Despite common carnitine supplement consumption among athletes for improved exercise performance or recovery, there is insufficient high-quality clinical evidence to indicate it provides any benefit. Biosynthesis and metabolism
Many eukaryotes have the ability to synthesize carnitine, including humans. Humans synthesize carnitine from the substrate TML (6-N-trimethyllysine), which is in turn derived from the methylation of the amino acid lysine. TML is then hydroxylated into hydroxytrimethyllysine (HTML) by trimethyllysine dioxygenase (TMLD), requiring the presence of ascorbic acid and iron.
But before the target cells can use the fatty acids for ATP production and β oxidation, the fatty acids with chain lengths of 14 or more carbons must be activated and subsequently transported into mitochondrial matrix of the cells in three enzymatic reactions of the carnitine shuttle.The first reaction of the carnitine shuttle is a two-step process catalyzed by a family of isozymes of acyl-CoA synthetase that are found in the outer mitochondrial membrane, where they promote the activation of fatty acids by forming a thioester bond between the fatty acid carboxyl group and the thiol group of coenzyme A to yield a fatty acyl–CoA.In the first step of the reaction, acyl-CoA synthetase catalyzes the transfer of adenosine monophosphate group (AMP) from an ATP molecule onto the fatty acid generating a fatty acyl–adenylate intermediate and a pyrophosphate group (PPi). The pyrophosphate, formed from the hydrolysis of the two high-energy bonds in ATP, is immediately hydrolyzed to two molecules of Pi by inorganic pyrophosphatase. This reaction is highly exergonic which drives the activation reaction forward and makes it more favorable. In the second step, the thiol group of a cytosolic coenzyme A attacks the acyl-adenylate, displacing AMP to form thioester fatty acyl-CoA.In the second reaction, acyl-CoA is transiently attached to the hydroxyl group of carnitine to form fatty acylcarnitine.