L-Carnitine (levocarnitine) is an amino acid that is vital to mitochondrial utilization of fatty acids. It is an orphan drug approved by the Food and Drug Administration for treatment of L-carnitine deficiency that results from inborn errors of metabolism, is associated with hemodialysis, occurs secondary to valproic acid toxicity, and for zidovudine (AZT)-induced mitochondrial myopathy10,11,20 and pediatric cardiomyopathy.17
L-Carnitine decreases valproic acid–induced hyperammonemia and limits valproic acid–induced hepatic toxicity. L-Carnitine should be administered intravenously (IV) to symptomatic patients because of the limited bioavailability after oral (PO) administration.
L-Carnitine is found in mammals, in many bacteria, and in very small amounts in most plants.37 Carnitine was first discovered in 1905 in extracts of muscle, and its name is derived from carnis, the Latin word for flesh.21 Over the next 25 years, its chemical formula and structure were identified, and in 1997, its enantiomeric properties were confirmed.37 Carnitine was formerly known as vitamin BT.
Carnitine is a water-soluble amino acid that can exist as either the d or L form; however, the L isomer, which is found endogenously, is active and should be used therapeutically. L-Carnitine (C7H15NO3) has a molecular weight of 161 daltons. At physiologic pH, L-carnitine contains both a positively charged quaternary nitrogen ion and a negatively charged carboxylic acid group.15
Fatty acids provide 9 kcal/g and are an important source of energy for the body, especially for the liver, heart, and skeletal muscle. The utilization of fatty acids as an energy source requires L-carnitine–mediated passage through both the outer and inner mitochondrial membranes to reach the mitochondrial matrix where β-oxidation occurs (see Figs. 47-2 and 12-8). Enzymes in the outer and inner mitochondrial membranes (carnitine palmitoyltransferase and carnitine acylcarnitine translocase) catalyze the synthesis, translocation, and regeneration of L-carnitine.33 Binding of L-carnitine to fatty acids occurs through esterification at the hydroxyl group on the chiral carbon.15 The L-carnitine regenerated in the mitochondrial matrix can also translocate in the opposite direction, from the matrix and through the inner membrane back to the space between the outer and inner membrane. Acyl-coenzyme A (CoA) is transported by carnitine from the cytosol to the mitochondria and undergoes β-oxidation in the mitochondrial matrix, generating acetyl-CoA, which then enters the citric acid cycle for the generation of adenosine triphosphate (ATP).
Approximately 54% to 87% of the body stores of L-carnitine is derived primarily from meat and dairy products in the diet; the remainder is synthesized.37 Although most plants supply very little L-carnitine, avocado and fermented soy products are exceptionally rich in this amino acid. The remainder of the carnitine needed by the body is synthesized from trimethyllysine. This amino acid, found largely in skeletal muscle, is converted to trimethylammoniobutanoate (γ-butyrobetaine) and ...