Characterization of Na(+)-independent glutamine transport in rat liver.

In hepatic plasma membrane vesicles (HPMVs) from rat liver, we observed that approximately 40-45% of Na(+)-independent glutamine uptake occurs by a saturable carrier-mediated process. This component of glutamine uptake is mediated by a transport agency distinct from that of previously described systems for the Na(+)-independent transport of amino acids. Transport of glutamine was electroneutral and occurred into an osmotically active space with negligible membrane binding. The model system L substrate 2-amino-2-norbornane-carboxylic acid (BCH) showed no appreciable inhibition of Na(+)-independent glutamine uptake by HPMVs but effectively inhibited the uptake of leucine, a classic system L substrate, in identical vesicle preparations. Further evidence against system L-mediated glutamine transport was provided by the pH dependence and the lack of trans-stimulation of saturable uptake. Competition experiments with selected amino acids revealed a pattern of inhibition of glutamine transport that was inconsistent with assignment of glutamine entry to systems asc, T, or systems for the Na(+)-independent transport of the charged amino acids. This BCH-noninhibitable transport system in HPMVs was highly selective for glutamine, histidine, and, to a lesser extent, asparagine. Inhibition of Na(+)-independent glutamine transport by leucine was noncompetitive in nature. On the basis of Na+ independence, pH sensitivity, absence of trans-stimulation, and an amino acid selectivity similar to that of the previously described hepatic Na(+)-dependent system N, we have provisionally designated the glutamine transport agency described in this article as system "n."