Carnitine precursor γ-butyrobetaine is a novel substrate of the Na⁺ and Cl^–-dependent GABA transporter Gat2

Abstract

  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 (d₃-GBB) by Xenopus oocytes expressing rGat2. rGat2-mediated d₃-GBB uptake was Na⁺ and Cl^–-dependent and saturable with K_m of 70.6 ± 34.8 µM. In carnitine transporter Octn2-deficient Jvs mice, mRNA expression of mGat3, the mouse orthologue of GAT2, was decreased in liver, but increased in brain, while mRNA expression of mBbox1, which hydroxylates GBB to carnitine, increased in kidneys and brain. These results indicate that Gat2 plays a role in transmembrane transport of GBB.