Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2

Ikumi Tamai, Rikiya Ohashi, Jun Ichi Nezu, Hikaru Yabuuchi, Asuka Oku, Miyuki Shimane, Yoshimichi Sai, Akira Tsujit

研究成果: ジャーナルへの寄稿学術論文査読

646 被引用数 (Scopus)

抄録

Primary carnitine deficiency, because of a defect of the tissue plasma membrane carnitine transporters, causes critical symptoms. However, the transporter has not been molecularly identified. In this study, we screened a human kidney cDNA library and assembled a cDNA-encoding OCTN2 as a homologue of the organic cation transporter OCTN1, and then we examined the function of OCTN2 as a carnitine transporter. OCTN2-cDNA encodes a polypeptide of 557 amino acids with 75.8% similarity to OCTN1. Northern blot analysis showed that OCTN2 is strongly expressed in kidney, skeletal muscle, heart, and placenta in adult humans. When OCTN2 was expressed in HEK293 cells, uptake of L-[3H]carnitine was strongly enhanced in a sodium-dependent manner with K(m) value of 4.34 μM, whereas typical substrates for previously known organic cation transporters, tetraethylammonium and guanidine, were not good substitutes. OCTN2-mediated L-[3H]carnitine transport was inhibited by the D-isomer, acetyl-D,L-carnitine, and γ-butyrobetaine with high affinity and by glycinebetaine with lower affinity, whereas choline, β-hydroxybutyric acid, γ-aminobutyric acid, lysine, and taurine were not inhibitory. Because the observed tissue distribution of OCTN2 is consistent with the reported distribution of carnitine transport activity and the functional characteristics of OCTN2 coincide with those reported for plasma membrane carnitine transport, we conclude that OCTN2 is a physiologically important, high affinity sodium-carnitine cotransporter in humans.

本文言語英語
ページ(範囲)20378-20382
ページ数5
ジャーナルJournal of Biological Chemistry
273
32
DOI
出版ステータス出版済み - 07-08-1998

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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