Distribution and metabolism of 14C-tryptophan in normal and endotoxin-poisoned mice

dl-Tryptophan (benzene ring-(14)C) and its metabolites persist longer and in greater quantity in tissues of endotoxin-poisoned mice than in tissues of normal mice. Correspondingly less label is excreted in urine and feces and expired as (14)CO(2) in the poisoned animals. The distribution of label (1.1 x 10(6) dpm per microgram of tryptophan) was relatively constant whether it was administered alone or in combination with 20 mg of unlabeled l-tryptophan. Tryptophan must be metabolized through the tryptophan oxygenase pathway to be converted to carbon dioxide, but attempts to quantitatively correlate depressed tryptophan oxygenase activity with depressed carbon dioxide production were unsuccessful. It appears that neither tryptophan oxygenase nor substrate availability exclusively determine the quantity of tryptophan converted to (14)CO(2) except under highly selected conditions. The validity of an earlier suggestion that expired (14)CO(2) could be used to monitor in vivo tryptophan oxygenase activity is not supported by our data.