Journal
DRUG METABOLISM AND PHARMACOKINETICS
Volume 26, Issue 6, Pages 632-636Publisher
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.DMPK-11-NT-053
Keywords
gamma-butyrobetaine; carnitine; GABA; GAT2; juvenile visceral steatosis (Jvs); OCTN2; transporter
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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 mu M. 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.
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