The effects of salicylate on the activity of rat liver tryptophan pyrrolase in vitro and in vivo.

1. Salicylate, in concentrations of 0.05mm and above, inhibits the basal activity of tryptophan pyrrolase in homogenates of rat liver and the activity induced by cortisol but not that induced by tryptophan. The inhibition is abolished by adding haematin to the reaction mixtures. 2. The intraperitoneal injection of 400mg of sodium salicylate/kg in the rat causes a decrease in the tryptophan pyrrolase activity in the liver at 30min, the activity is restored to normal at 2h, increases to sixfold after 5h and returns to the basal value at 12h. The activation of the enzyme by salicylate is prevented by the administration of cycloheximide but not by pretreatment with actinomycin D. The effects of the combined injection of salicylate and cortisol are additive, whereas those of salicylate plus tryptophan are not. The injection of salicylate causes a progressive increase in the holo-/apo-enzyme ratio and an increased content of tryptophan in the liver over a period of 3h. 3. It is suggested that salicylate inhibits tryptophan pyrrolase activity in vitro and in vivo by interacting with iron protoporphyrins and causes a later enhancement of the enzyme activity in vivo by a mechanism involving the release of tryptophan from its binding sites on circulating albumin and on other proteins.