Tryptophan oxugenase and tryptophan metabolism in endotoxin-poisoned and allopurinol-treated mice

Abstract

Endotoxin-poisoned mice frequently die in convulsions withing 4–8 h after a delayed, but not concurrent, injection of tryptophan. Following injection of endotoxin into CF-1 mice tryptophan oxygenase (EC 1.13.1.12) activity was initially increased but by 10 h showed approx. 50% inhibition. CF-1 mice were sensitive to tryptophan only when tryptophan oxygenase was depressed, i.e. after 10 h. If the early increase in tryptophan oxygenase was blocked by allopurinol, mice showed sensitivity to tryptophan within only 4 h after endotoxin. Mice given allopurinol alone were not sensitive to tryptophan even though tryptophan oxygenase was depressed. If tryptophan oxygenase activity was elevated by injection of α-methyltryptophan 8 h after endotoxin, no sensitivity to tryptophan was observed at the 10-h time period. Collectively these data indicate that tryptophan oxygenase activity must be depressed for endotoxin-poisoned mice to show sensitivity to tryptophan but that depressed tryptophan oxygenase per se does not increase toxicity of tryptophan in normal animals.