Tamai I, Ohashi R, Nezu J I, Sai Y, Kobayashi D, Oku A, Shimane M, Tsuji A
Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-0934, Japan.
J Biol Chem. 2000 Dec 22;275(51):40064-72. doi: 10.1074/jbc.M005340200.
Carnitine is essential for beta-oxidation of fatty acids, and a defect of cell membrane transport of carnitine leads to fatal systemic carnitine deficiency. We have already shown that a defect of the organic cation/carnitine transporter OCTN2 is a primary cause of systemic carnitine deficiency. In the present study, we further isolated and characterized new members of the OCTN family, OCTN1 and -3, in mice. All three members were expressed commonly in kidney, and OCTN1 and -2 were also expressed in various tissues, whereas OCTN3 was characterized by predominant expression in testis. When their cDNAs were transfected into HEK293 cells, the cells exhibited transport activity for carnitine and/or the organic cation tetraethylammonium (TEA). Carnitine transport by OCTN1 and OCTN2 was Na(+)-dependent, whereas that by OCTN3 was Na(+)-independent. TEA was transported by OCTN1 and OCTN2 but not by OCTN3. The relative uptake activity ratios of carnitine to TEA were 1.78, 11.3, and 746 for OCTN1, -2, and -3, respectively, suggesting high specificity of OCTN3 for carnitine and significantly lower carnitine transport activity of OCTN1. Thus, OCTN3 is unique in its limited tissue distribution and Na(+)-independent carnitine transport, whereas OCTN1 efficiently transported TEA with minimal expression of carnitine transport activity and may have a different role from other members of the OCTN family.
肉碱对于脂肪酸的β氧化至关重要，而肉碱细胞膜转运缺陷会导致致命的全身性肉碱缺乏症。我们已经表明，有机阳离子/肉碱转运体OCTN2的缺陷是全身性肉碱缺乏症的主要原因。在本研究中，我们进一步在小鼠中分离并鉴定了OCTN家族的新成员OCTN1和OCTN3。所有这三个成员在肾脏中均有共同表达，OCTN1和OCTN2也在各种组织中表达，而OCTN3的特征是在睾丸中占主导性表达。当它们的cDNA转染到HEK293细胞中时，这些细胞表现出对肉碱和/或有机阳离子四乙铵（TEA）的转运活性。OCTN1和OCTN2介导的肉碱转运是Na⁺依赖性的，而OCTN3介导的肉碱转运是Na⁺非依赖性的。TEA可由OCTN1和OCTN2转运，但不能由OCTN3转运。OCTN1、OCTN2和OCTN3对肉碱与TEA的相对摄取活性比值分别为1.78、11.3和746，这表明OCTN3对肉碱具有高特异性，而OCTN1的肉碱转运活性明显较低。因此，OCTN3在其有限的组织分布和Na⁺非依赖性肉碱转运方面具有独特性，而OCTN1以最低的肉碱转运活性高效转运TEA，可能与OCTN家族的其他成员具有不同的作用。
