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 water-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 beta-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 acetylcarnitine, increases during diabetic ketoacidosis, fasting, and physical activity, particularly high-intensity exercise. Plasma concentration of free L-carnitine decreases simultaneously under these conditions. (C) 2017 IUBMB Life