Abstract
L-Carnitine (β-hydroxyl-γ-trimethylaminobutyric acid) acts as an essential cofactor for β-oxidation of long-chain fatty acids by facilitating the transport of fatty acid across the inner membranes of mitochondria as acylcarnitine esters. OCTN2 (SLC22A5) was first isolated as a novel organic cation transporter with high homology to OCTN1 (SLC22A4). OCTN2 has a high affinity for carnitine and acylcarnitine and efficiently transports them in Na^+-dependent manner. Mutation of OCTN2 leads to primary systemic carntine deficiency (SCD; OMIM 212140). SCD is an autosomal recessive disorder characterized by progressive cardiomyopathy, skeletal myopathy, hypoglycemia and hyperammonaemia. Several pharmacokinetic studies using a SCD model mouse, jvs (juvenile visceral steatosis), have revealed that OCTN2 governs carntine disposition in vivo. OCTN2 is involved in the efficient reabsorption of carntine in renal tubular epithelial cells. OCTN2 also function as the uptake transporter in the intestine, the heart, the liver and male reproduction system.
