Coupled and uncoupled proton movement by amino acid transport system N

The system N transporter SN1 has been proposed to mediate the efflux of glutamine from cells required to sustain the urea cycle and the glutamine-glutamate cycle that regenerates glutamate and γ-aminobutyric acid (GABA) for synaptic release. We now show that SN1 also mediates an ionic conductance activated by glutamine, and this conductance is selective for H⁺. Although SN1 couples amino acid uptake to H⁺ exchange, the glutamine-gated H⁺ conductance is not stoichiometrically coupled to transport. Protons thus permeate SN1 both coupled to and uncoupled from amino acid flux, providing novel mechanisms to regulate the transfer of glutamine between cells.