bound., Mechanism Early proposals for the mechanism of tryptophan oxidation were presented by Sono and Dawson. This suggested a base-catalysed abstraction mechanism, involving only the ferrous (FeII) heme. It is assumed that TDO and IDO react by the same mechanism, although there is no concrete evidence for that. In IDO, a ferryl heme (FeIV) has been identified during turnover. Mechanistic proposals have therefore been adjusted to include the formation of ferryl heme during the mechanism. TDO is assumed to react in the same way, but a ferryl heme has not been observed in TDO. See also discussion of mechanism for indoleamine 2,3-dioxygenase. Clinical significance It has been shown that tryptophan 2,3-dioxygenase is expressed in a significant proportion of human tumors. In the same study, tryptophan 2,3-dioxygenase expression by tumors prevented their rejection by immunized mice. A tryptophan 2,3-dioxygenase inhibitor developed by the group restored the ability of these mice to reject tryptophan 2,3-dioxygenase-expressed tumors, demonstrating that tryptophan 2,3-dioxygenase inhibitors display potential in cancer therapy. Another study showed that tryptophan 2,3-dioxygenase is potentially involved in the metabolic pathway responsible for anxiety-related behavior. Generating mice deficient for tryptophan 2,3-dioxygenase and comparing them to the wild type, the group found that the tryptophan 2,3-dioxygenase-deficient mice showed increased plasma levels not only of tryptophan, but also of serotonin and 5-HIAA in the hippocampus and midbrain. A variety of tests, such as elevated plus maze and open-field tests showed anxiolytic modulation in these knock-out mice, the findings demonstrating a direct link between tryptophan 2,3-dioxygenase and tryptophan metabolism and anxiety-related behavior under physiological conditions. See also Heme Indoleamine 2,3-dioxygenase Kynurenine Tryptophan References Further reading EC 1.13.11 Heme enzymes Enzymes of known structure