Role of cell permeability in the metabolism of histidine and urocanic acid

Abstract

Both in vivo and in vitro tests with radioactively labeled histidine and urocanic acid showed that rat liver tissue is more readily permeable to histidine than to urocanic acid. Total urinary output of urocanic acid and its radioactivity were measured after the administration of l-histidine by stomach tube and of urocanic acid by subcutaneous injection (one labeled; the other unlabeled) in rats which had previously been fed normal diets or diets supplemented with 0.05% of dl-ethionine. Labeling only the histidine or only the urocanic acid made it possible to determine the contribution of each to the urocanic acid output. In the normal animal both preformed urocanic acid which enters the cell and urocanic acid produced in it can be further metabolized. In the ethionine-fed animal further metabolism is limited by the inhibition of urocanase, and urocanic acid accumulates within the cell. The accumulation resists the entrance of extracellular urocanic acid, which in turn checks the excretion of cellular urocanic acid and its further production from histidine. The data provide a rational basis for reconciling the limited glycogen production induced by urocanic acid with the concept that urocanic acid is nevertheless a significant intermediate in the histidine-glycogen pathway.