Characterization of Sodium–Dependent Amino Acid Transport Activity During Liver Regeneration

Abstract

Liver regeneration occurs after removal of or damage to a portion of the liver; it leads to restoration of the original liver mass. The activities of three sodium-dependent amino acid transporters--system A, system N and system ASC--were determined during a 5-day period of liver regeneration in the rat. Seventy-percent hepatectomy or laparotomy was performed in pairs of rats; these rats' livers were removed at different time points after surgery. Transport activity was determined through measurement of the Na(+)-dependent uptake of tritiated amino acids by isolated hepatic plasma membrane vesicles. System A activity, as measured by the Na(+)-dependent uptake of 2-aminoisobutyric acid, is increased in the regenerating liver 2 to 24 hr after surgery compared with that of controls. Kinetic analysis of 2-(methylamino)isobutyric acid uptake showed a 100% increase in the maximum velocity of system A transport in the hepatectomized animals with no change in the Michaelis constant, suggesting an increase in the number of system A transport proteins in the plasma membrane of regenerating liver. During liver regeneration, no changes were noted in the transport activities of system N and system ASC as measured by the uptake of glutamine and cysteine, respectively, in the presence of 2-(methylamino)isobutyric acid. Our work suggests that system A performs a unique role in the secondary active transport of its substrate neutral amino acids to meet the metabolic demands of regenerating liver.