Department of Membrane Transport and Biopharmaceutics, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Japan.
Drug Metab Pharmacokinet. 2011;26(6):632-6. doi: 10.2133/dmpk.dmpk-11-nt-053. Epub 2011 Oct 12.
To study transport of the carnitine precursor gamma-butyrobetaine (GBB) by rat liver-specific GABA transporter 2 (rGat2), we measured the uptake of deuterated GBB (d(3)-GBB) by Xenopus oocytes expressing rGat2. rGat2-mediated d(3)-GBB uptake was Na(+) and Cl(-) dependent, and was saturable with a K(m) value of 70.6 ± 34.8 µM. In carnitine transporter Octn2-deficient Jvs mice, mRNA expression of mGat3, the mouse ortholog of GAT2, decreased in liver, but increased in brain, while mRNA expression of mBbox1, which hydroxylates GBB to carnitine, increased in kidney and brain. These results indicate that GAT2 plays a role in transmembrane transport of GBB.
为了研究肉碱前体γ-丁氧基甜菜碱（GBB）通过大鼠肝脏特异性 GABA 转运体 2（rGat2）的转运，我们测量了表达 rGat2 的非洲爪蟾卵母细胞对氘代 GBB（d（3）-GBB）的摄取。rGat2 介导的 d（3）-GBB 摄取依赖于 Na（+）和 Cl（-），并且对 K（m）值为 70.6±34.8µM 呈饱和状态。在肉碱转运体 Octn2 缺陷型 Jvs 小鼠中，mGat3（GAT2 的小鼠同源物）的 mRNA 表达在肝脏中降低，但在大脑中增加，而将 GBB 羟基化为肉碱的 mBbox1 的 mRNA 表达在肾脏和大脑中增加。这些结果表明 GAT2 在 GBB 的跨膜转运中发挥作用。
