Relationship between L-tryptophan uptake and L-tryptophan 2,3-dioxygenase activity in rat hepatocytes

The relationship between L-tryptophan uptake and tryptophan 2,3-dioxygenase activity in hepatocytes was examined and compared with the change of hepatic L-leucine, L-phenylalanine, and L-tyrosine uptakes using isolated hepatocytes of rats in which the oxygenase was induced with L-tryptophan or hydrocortisone. In L-tryptophan- or hydrocortisone-treated rat hepatocytes, the rate of L-tryptophan uptake into hepatocytes via the saturable high-affinity transport component significantly increased but the hepatic uptake rate of L-leucine did not change at all. In hydrocortisone-treated rat hepatocytes, a little stimulated hepatic uptake of L-phenylalanine or L-tyrosine was observed. In the stimulated hepatic uptake of L-tryptophan via the high-affinity transport component, the Km value did not change but the Vmax value increased. Liver plasma membranes prepared from rats treated with L-tryptophan or hydrocortisone showed the same binding rate of L-tryptophan to the membranes as those from control rats. In addition, hepatic L-tryptophan uptake via the high-affinity transport component correlated well with hepatic tryptophan 2,3-dioxygenase activity (r = 0.787). The present results indicate that the uptake of L-tryptophan into hepatocytes via a transport system which works under physiological conditions is closely related to hepatic tryptophan 2,3-dioxygenase activity.