l-Carnitine (levocarnitine) is an amino acid vital to mitochondrial utilization of fatty acids. It is approved by the US Food and Drug Administration (FDA) for treatment of l-carnitine deficiency that either results from inborn errors of metabolism or is associated with hemodialysis. l-Carnitine is also used off label to treat carnitine deficiency secondary to valproic acid toxicity or that associated with zidovudine (AZT)-induced mitochondrial myopathy10,11,19 and pediatric cardiomyopathy.17
Based on the proposed mechanism of action of valproic acid–induced hyperammonemia and valproic acid–induced hepatic toxicity, l-carnitine should theoretically help with both of these conditions, but the data to support this are limited. Based on the available evidence, l-carnitine should be considered for patients with valproic acid–induced hyperammonemia and valproic acid–induced hepatic toxicity. Symptomatic patients should receive l-carnitine intravenously; because of limited bioavailability, oral administration should be reserved for patients who are not acutely ill.
l-Carnitine is found in mammals, in many bacteria, and in very small amounts in most plants except for avocado and soy products.36 Carnitine was first discovered in 1905 in extracts of muscle, and its name is derived from carnis, the Latin word for flesh.20 Subsequently, its chemical formula and structure were identified, and in 1997, its enantiomeric properties were confirmed.36 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 endogenous l isomer is the active form and should be used therapeutically. l-Carnitine (C7H15NO3) has a molecular weight of 161 Da. 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 important sources of human energy for the body, particularly 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 (Figs. 48–2 and 13–9). Enzymes in the outer and inner mitochondrial membranes (carnitine palmitoyltransferase and carnitine acylcarnitine translocase) catalyze the synthesis, translocation, and regeneration of l-carnitine.32 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 intermembrane space. 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 ...