Surprising differences in substrate selectivity and other properties of systems A and ASC between rat hepatocytes and...

We find that the two wide-range Na+-dependent transport systems A and ASC for various neutral amino acid can be discriminated more sharply in the hepatoma cell line HTC than in any cell yet studied by us in which the two systems co-exist. The gain comes partly from a higher reproducibility and a higher relative ASC rate for HTC than in ordinary rat hepatocytes, also a repressed condition of System A unless first deprived of amino acids, but mainly from our finding that in the hepatoma cell threonine serves as a nearly specific substrate and inhibitor of System ASC, thus decisively supplementing older discriminatory techniques. In ordinary hepatocytes cysteine is quite specific to ASC as a substrate but not as an inhibitor, whereas threonine is specific in neither role. In the hepatoma cell cysteine in turn is specific in neither role. In addition to these and other differences between the two cells in analog specificity, which are partly assignable to System ASC and partly to System A, System ASC of the hepatoma cell shows an inhibition on lowering the pH from 6.5 to 5 not seen in the ordinary hepatocyte. Furthermore, threonine uptake by the hepatoma cell undergoes no stimulation when Li+ is substituted for choline in a Na+-free medium, whereas ASC uptake by the ordinary rat hepatocyte is stimulated much as is System A uptake. As in other occurrences, and in contrast to System A, ASC transport in the hepatoma cell is stimulated neither by amino acid deprivation nor by insulin, glucagon, or dexamethasone. Trans-stimulation, both inward and outward, via System ASC is vigorous in the hepatoma cell. Despite the surprising differences observed, common features of each system in various occurrences continue to justify the use of the abbreviations ASC and A as long as they are understood as generic designations.