Figure 1. L-carnitine biosynthesis.

L-carnitine can be partly provided by an omnivorous diet/fish and meat in the diet, but the required levels can also be synthesized from the amino acids L-lysine and L-methionine. L-carnitine biosynthesis takes place mainly in skeletal muscle, kidney and liver. Lysine is methylated three times by a methyltransferase that uses S-adenosyl-L-methionine as methyl group donor [42], [43]. This gives protein-linked 6-N-trimethyllysine, which is released by protein breakdown, the rate-limiting step in L-carnitine biosynthesis [44]. The major proportion of 6-N-trimethyllysine is found in skeletal muscle (65%), which quantitatively is the most important organ in L-carnitine synthesis. The next step, hydroxylation of trimethyllysine to 3-hydroxy-6-N-trimethyllysine (by 6-N-trimethyllysine hydroxylase) takes place in the mitochondria, with especially high enzyme activity in kidney but also in liver, skeletal muscle, heart and brain [45], [46]. The enzymes involved in cleavage of 3-hydroxy-6-N-trimethyllysine into glycine and 4-trimethylaminobutyraldehyde/γ-butyrobetainaldehyde (3-hydroxy-6-N-trimethyllysine aldolase), and subsequently to γ-butyrobetaine (4-trimethylaminobutyraldehyde dehydrogenase) has highest activity in the liver of rodents, and in the liver and kidney of humans. Finally, γ-butyrobetaine hydroxylase is involved in the formation of L-carnitine in the liver of rodents, and in the liver and kidney of humans [47].