The organic cation/carnitine transporter OCTN2 transports carnitine in a sodium-dependent manner, whereas it transports organic cations sodium-independently. To elucidate the functional domain in OCTN2, we constructed chimeric proteins of human OCTN2 (hOCTN2) and mouse OCTN3 (mOCTN3) and introduced mutations at several amino acids conserved among human, rat and mouse OCTN2. We found that transm...

INTRODUCTION Carnitine is an essential cofactor in mitochondrial fatty acid oxidation. Carnitine deficiency results in accumulation of non-oxidized fatty acyl-coenzyme A molecules, and this inhibits intra-mitochondrial degradation of ammonia. Hyperammonemia may lead to encephalopathy. This scenario has been previously reported. CASE PRESENTATION We report the case of a 47-year-old Caucasian m...

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well tolerated, but rare serious complications may occur in some patients receiving VPA chronically, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy (VHE). Some data suggest that VHT and VHE may be promoted by carnitine deficienc...

Choline is an essential nutrient, and choline deficiency has been associated with cardiovascular morbidity. Choline is also the precursor of acetylcholine (cholinergic component of the heart's autonomic nervous system), whose levels are regulated by acetylcholinesterase (AChE). Cardiac contraction-relaxation cycles depend on ion gradients established by pumps like the adenosine triphosphatases ...

Carnitine is a small molecule widely present in all cells from prokaryotic to eukaryotic. It is an important element in β-oxidation of fatty acids. Carnitine is a scavenger of oxygen free radicals in mammalian tissues. Lack of carnitine in a hemodialysis patient can lead to carnitine deficiency. Oxidation of fatty acids and lipid metabolism are severly affected by carnitine deficiency. Oxidativ...

Carnitine is a metabolic cofactor which is essential for normal fatty acid metabolism. Patients with chronic kidney disease on dialysis have been shown both to suffer from disordered fatty acid metabolism and to have a significant deficiency in plasma and tissue carnitine. Aberrant fatty acid metabolism has been associated with a number of cellular abnormalities such as increased mitochondrial ...

Meldonium (mildronate; 3-(2,2,2-trimethylhydrazinium)propionate; THP; MET-88) is a clinically used cardioprotective drug, which mechanism of action is based on the regulation of energy metabolism pathways through l-carnitine lowering effect. l-Carnitine biosynthesis enzyme γ-butyrobetaine hydroxylase and carnitine/organic cation transporter type 2 (OCTN2) are the main known drug targets of meld...

BACKGROUND The clinical manifestations of inherited disorders of fatty acid oxidation vary according to the enzymatic defect. They may present as isolated cardiomyopathy, sudden death, progressive skeletal myopathy, or hepatic failure. Arrhythmia is an unusual presenting symptom of fatty acid oxidation deficiencies. METHODS AND RESULTS Over a period of 25 years, 107 patients were diagnosed wi...