Carnitine

Authors: ODLE, JACK - North Carolina State University; Adams, Sean; VOCKLEY, JERRY - University Of Pittsburgh

Submitted to: Advances in Nutrition
Publication Type: Review Article
Publication Acceptance Date: 3/1/2014
Publication Date: 6/5/2014
Citation: Odle, J., Adams, S.H., Vockley, J. 2014. Carnitine. Advances in Nutrition. 5:289-290. DOI:10.3945/an.113.005199.

Interpretive Summary: Carnitine (L-g-trimethylamino-ß-hydroxybutyrate) functions metabolically as a covalent molecular chaperone of acyl compounds esterified to its hydroxyl moiety (1,2). The quintessentialmetabolic function of L-carnitine is to shuttle long-chain FAs (LCFAs)2 across the inner mitochondrial membrane to their primary site of ß-oxidation within the mitochondrial matrix. The transfer of acyl compounds from CoA-esters to carnitine also serves to regenerate cellular-free CoA that is essential for intermediary metabolism. Synthesis of acylcarnitines is catalyzed by a family of carnitine O-acyltransferase enzymes (EC 2.3.1.21, EC 2.3.1.137, and EC 2.3.1.7) that transfer the acyl group from acyl-CoA to form acylcarnitine. The acylcarnitines can then be transported across cell-surface [organic cation transporter; solute carrier family 22 (organic cation/carnitine transporter), member A5 (SLC22A5), organic cation transporter number 2] and inner mitochondrial (carnitine–acylcarnitine translocase; SLC25A20) membranes via specific transporters. Carnitine is very high in red meat (up to 80 µg/100g), intermediate in dairy products, and low-to-nonexistent in vegetable foods. The L-isomer is synthesized commercially, and dietary supplements of high purity are available and are generally recognized as safe. Currently, carnitine has no established dietary reference intakes. Carnitine can be classified as a conditionally essential nutrient, meaning that, although most individuals can synthesize enough to meet their metabolic needs, under some circumstances, endogenous synthesis is inadequate. In particular, developing neonates may require dietary carnitine, asmay patients with selected inherited disorders, individuals on a strict vegan diet, and patients on dialysis. The pathway of de novo synthesis is limited by the release of trimethyl-lysine during protein turnover and involves several enzymatic reactions involving other essential nutrients, including vitamin C, iron, niacin, and vitamin B-6. Because the last step in the pathway ('-butyrobetaine hydroxylase) is limited to liver, kidney, and brain, other tissues must obtain carnitine from circulation.

Technical Abstract: Carnitine (L-g-trimethylamino-ß-hydroxybutyrate) functions metabolically as a covalent molecular chaperone of acyl compounds esterified to its hydroxyl moiety (1,2). The quintessentialmetabolic function of L-carnitine is to shuttle long-chain FAs (LCFAs)2 across the inner mitochondrial membrane to their primary site of ß-oxidation within the mitochondrial matrix. The transfer of acyl compounds from CoA-esters to carnitine also serves to regenerate cellular-free CoA that is essential for intermediary metabolism. Synthesis of acylcarnitines is catalyzed by a family of carnitine O-acyltransferase enzymes (EC 2.3.1.21, EC 2.3.1.137, and EC 2.3.1.7) that transfer the acyl group from acyl-CoA to form acylcarnitine. The acylcarnitines can then be transported across cell-surface [organic cation transporter; solute carrier family 22 (organic cation/carnitine transporter), member A5 (SLC22A5), organic cation transporter number 2] and inner mitochondrial (carnitine–acylcarnitine translocase; SLC25A20) membranes via specific transporters. Carnitine is very high in red meat (up to 80 µg/100g), intermediate in dairy products, and low-to-nonexistent in vegetable foods. The L-isomer is synthesized commercially, and dietary supplements of high purity are available and are generally recognized as safe. Currently, carnitine has no established dietary reference intakes. Carnitine can be classified as a conditionally essential nutrient, meaning that, although most individuals can synthesize enough to meet their metabolic needs, under some circumstances, endogenous synthesis is inadequate. In particular, developing neonates may require dietary carnitine, asmay patients with selected inherited disorders, individuals on a strict vegan diet, and patients on dialysis. The pathway of de novo synthesis is limited by the release of trimethyl-lysine during protein turnover and involves several enzymatic reactions involving other essential nutrients, including vitamin C, iron, niacin, and vitamin B-6. Because the last step in the pathway ('-butyrobetaine hydroxylase) is limited to liver, kidney, and brain, other tissues must obtain carnitine from circulation.