Significance of l‐carnitine for human health

Carnitine acyltransferases catalyze the reversible transfer of acyl groups from acyl‐coenzyme A esters to l‐carnitine, forming acyl‐carnitine esters that may be transported across cell membranes. l‐Carnitine is a wáter‐soluble compound that humans may obtain both by food ingestion and endogenous synthesis from trimethyl‐lysine. Most l‐carnitine is intracellular, being present predominantly in liver, skeletal muscle, heart and kidney. The organic cation transporter‐2 facilitates l‐carnitine uptake inside cells. Congenital dysfunction of this transporter causes primary l‐carnitine deficiency. Carnitine acetyltransferase is involved in the export of excess acetyl groups from the mitochondria and in acetylation reactions that regulate gene transcription and enzyme activity. Carnitine octanoyltransferase is a peroxysomal enzyme required for the complete oxidation of very long‐chain fatty acids and phytanic acid, a branched‐chain fatty acid. Carnitine palmitoyltransferase‐1 is a transmembrane protein located on the outer mitochondrial membrane where it catalyzes the conversion of acyl‐coenzyme A esters to acyl‐carnitine esters. Carnitine acyl‐carnitine translocase transports acyl‐carnitine esters across the inner mitochondrial membrane in exchange for free l‐carnitine that exits the mitochondrial matrix. Carnitine palmitoyltransferase‐2 is anchored on the matrix side of the inner mitochondrial membrane, where it converts acyl‐carnitine esters back to acyl‐coenzyme A esters, which may be used in metabolic pathways, such as mitochondrial β‐oxidation. l‐Carnitine enhances nonoxidative glucose disposal under euglycemic hyperinsulinemic conditions in both healthy individuals and patients with type 2 diabetes, suggesting that l‐carnitine strengthens insulin effect on glycogen storage. The plasma level of acyl‐carnitine esters, primarily acetyl‐carnitine, increases during diabetic ketoacidosis, fasting, and physical activity, particularly high‐intensity exercise. Plasma concentration of free l‐carnitine decreases simultaneously under these conditions. © 2017 IUBMB Life, 69(8):578–594, 2017