Human tryptophan 2,3-dioxygenase

Induction of Tryptophan Dioxygenase by Glucocorticoid Hormones The de novo synthesis of tryptophan dioxygenase is induced by glucocorticoid hormones (cortisol in human beings and corticosterone in the rat). This is true induction of new mRNA and protein synthesis indeed. 

Indoleamine dioxygenase has been found in many tissues of mammals. It catalyzes the first and rate-limiting step in the main pathway of human tryptophan... 

In the rat, the most often studied animal species, whose tryptophan metabolism resembles closely that of humans, acute ethanol administration, as described earlier, induces a biphasic effect on serum tryptophan levels, an initial increase followed by a later inhibition. Similarly, acute ethanol administration exerts a biphasic effect on brain serotonin synthesis and turnover, an initial enhancement followed by a later inhibition.111 The initial enhancement is caused by an increase in circulating free tryptophan availability to brain, probably secondary to a catecholamine-dependent lipolysis and a nonesteri-fied fatty acid-mediated displacement of the albumin-bound amino acid, whereas the later inhibition of serotonin synthesis and turnover is the result of a decrease in circulating free and albumin-bound tryptophan availability to the brain secondary to activation of hepatic tryptophan 2,3-dioxygenase (TP) by the earlier increase in free tryptophan to the liver. The activation of hepatic TP by acute ethanol administration, which is substrate (tryptophan) mediated, has been described in rats by Badawy and Evans.111127128... 

Much information is available about the toxicity of L-tryptophan in humans and in animals. Generally, in humans the toxicity of L-tryptophan alone appears to be minimal. In animals, certain species appear to be more sensitive than others to L-tryptophan toxicity. Overall, these differences appear to be related to the animal s ability to metabolize tryptophan via tryptophan 2,3-dioxygenase species with high enzyme levels are less toxic in response to L-tryptophan administration. 

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