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J Biol Chem, Vol. 273, Issue 32, 20378-20382, August 7, 1998
From the 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 Km
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
Molecular and Functional Identification of Sodium
Ion-dependent, High Affinity Human Carnitine Transporter
OCTN2
,,,, and
Faculty of Pharmaceutical Sciences, Kanazawa
University, 13-1 Takara-machi, Kanazawa 920-0934, Japan and the
§ Chugai Research Institute for Molecular Medicine Inc.,
Ibaraki 300-4101, Japan
-butyrobetaine with high affinity and by glycinebetaine with lower affinity, whereas choline, 
-hydroxybutyric acid,
-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.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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|
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|
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|
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|
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|
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|
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|
|
 |
|
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|
|
|
|
 |
|
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|
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|
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