Identification of a low affinity, high capacity transporter of cationic amino acids in mouse liver

The liver regulates the supply of amino acids required for protein synthesis and intermediary metabolism between feeding and fasting in mammals. The flux of amino acids between the liver and other tissues is determined, in part, by the activity of specific carrier proteins. We have identified a carrier of the cationic amino acids arginine, lysine, and ornithine in mouse liver that is closely related to a previously identified transporter with the same substrate specificity expressed in nonhepatic tissues. Uptake studies were performed in Xenopus oocytes injected with cRNA encoding these proteins. The comparison of the two transporters in these studies demonstrated that, unlike the widely-expressed transporter, arginine uptake mediated by the liver carrier is significant only at substrate concentrations that exceed systemic plasma levels and is less dependent on the intracellular concentration of cationic amino acids. These properties enable hepatocytes expressing this carrier to remove excess cationic amino acids from the blood without interfering with their uptake by nonhepatic tissues that express the related transporter.