Cationic amino acid transport into cultured animal cells. II. Transport system barely perceptible in ordinary hepatocytes, but active in hepatoma cell lines.

The transport of cationic amino acids across the plasma membrane of several hepatoma cell lines (HTC, McA-RH7777, McA-RH8994, characterized in detail in the first of these) occurs by a saturable mediation which we designate System y+. Identical experiments with cultured rat hepatocytes usually yield nonsaturating kinetic cures. Accordingly, System y+ contributes little, if at all, to the flux of cationic amino acids in these cells. Analogous to the findings with other tissues, the influx of cationic amino acids into hepatoma cells is Na+- and pH-independent, stereoselective, inhibitable by neutral amino acids in the presence of Na+, and stimulated by cationic amino acids inside of the cell. This final characteristic, called trans-stimulation, is a kinetic property associated with the cationic amino acid transport system in all other eukaryotic cell types studied and provides evidence supporting the operation of System y+. Influx of cationic amino acids into hepatocytes displays no significant trans-stimulation which strongly suggests the absence or alteration of System y+ in this cell. Transport of arginine into hepatocytes is the rate-limiting step for its hydrolysis by arginase. Therefore, the relatively low influx of this amino acid under physiologic conditions due to the attenuation of System y+ activity apparently provides a kinetic barrier separating the extrahepatic arginine pool from the active cytoplasmic enzymes of the hepatic urea cycle. Such a separation may be required for the nutrition and survival of extrahepatic tissues.