GLUTAMINE TRANSPORT IN ISOLATED HUMAN HEPATOCYTES AND TRANSFORMED LIVER-CELLS

The transport of L-glutamine was examined in isolated adult and fetal human hepatocytes as well as in the human hepatoma cell lines HepG2 an d SK-Hep. In all cells studied, glutamine uptake was at least 85% Na+- dependent. Kinetic analysis of the Na+-dependent component indicated m ediation by a single transporter in three human hepatocyte preparation s and in SK-Hep cells, whereas two transporters appeared to be respons ible for glutamine uptake in HepG2 cells and in hepatocytes from the l iver of one male patient. Amino acid inhibition analysis showed primar y mediation by System N in fetal and adult hepatocytes, whereas System ASC was principally responsible for glutamine uptake in transformed c ells. Similar to the rat transporter, human System N was pH-sensitive, stereospecific, and responsive to treatment with steroid hormones. Al though the human carrier was less tolerant of Li+- for Na+ substitutio n, glutamine transport in primary human hepatocytes was stimulated by treatment with hypotonic buffer (cell swelling), as reported in rat pa renchymal cells. In contrast, glutamine transport in hepatoma cells wa s relatively insensitive to changes in extracellular pH and failed to show enhanced activity in response to hypoosmotic challenge. Collectiv ely, the data suggest that markedly distinct plasma membrane transport ers mediate the concentrative uptake of glutamine in normal and transf ormed human hepatocytes, and that the salient properties of System N h ave been largely conserved from rat to man.