Carnitine Biosynthesis and metabolism

Carnitine is a quaternary ammonium compound involved in the metabolism of most mammals, plants and some bacteria.To support energy metabolism, carnitine transports long-chain fatty acids into the mitochondria for oxidation to generate free energy and participates in the removal of metabolites from cells.Given its critical metabolic role, carnitine is concentrated in tissues such as skeletal and cardiac muscle, which metabolize fatty acids into energy sources.In general, individuals, including strict vegetarians, synthesize adequate levels of L-carnitine in their bodies.Carnitine exists as one of two stereoisomers (two enantiomers D-carnitine (S-(+)-) and L-carnitine (R-(−)-)). Both are biologically active, but only L-carnitine occurs naturally in animals, while D-carnitine is toxic because it inhibits the activity of L-carnitine.Pure carnitine is a white powder at room temperature and is a water-soluble zwitterion with relatively low toxicity.Derived from the amino acid,carnitine was first extracted from meat extracts in 1905, hence the name from the Latin "caro/carnis" or meat.Some people with genetic or medical disorders (such as premature babies) do not make enough carnitine and need dietary supplements.Despite the widespread consumption of carnitine supplements by athletes to improve athletic performance or recovery, there is insufficient high-quality clinical evidence to suggest 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 in turn is derived from the methylation of the amino acid lysine.TML is then hydroxylated to hydroxytrimethyllysine (HTML) by trimethyllysine dioxygenase (TMLD), requiring the presence of ascorbic acid and iron.HTML is then cleaved by HTML aldolase (HTMLA, an enzyme that requires pyridoxal phosphate) to produce 4-trimethylaminobutyraldehyde (TMABA) and glycine.TMABA is then dehydrogenated to γ-butylbetaine in an NAD+-dependent reaction, catalyzed by TMABA dehydrogenase.Then, γ-butylbetaine is hydroxylated to L-carnitine by γ-butylbetaine hydroxylase, a zinc-binding enzyme,requiring iron in the form of Fe2+.Carnitine is involved in the transport of fatty acids across the mitochondrial membrane by forming long-chain acetylcarnitine esters and transported by carnitine palmitoyltransferase I and carnitine palmitoyltransferase II.Carnitine also plays a role in stabilizing acetyl-CoA and CoA levels through its ability to accept or donate acetyl groups.

Tissue distribution of carnitine biosynthetic enzymes

Tissue distribution of carnitine biosynthetic enzymes in humans shows that TMLD is most active in liver, heart, muscle, brain and kidney.

HTMLA activity is primarily found in the liver.TMABA oxidation rates are highest in the liver and also have considerable activity in the kidneys.