Is Indoleamine 2,3-Dioxygenase Another Heme and Copper Containing Enzyme?
Indoleamine 2,3-dioxygenase catalyzes a reaction similar to that catalyzed by L-tryptophan 2,3-dioxygenases except that the former shows little substrate specificity while the latter shows absolute specificity for L-tryptophan. Originally referred to as D-tryptophan oxygenase, indoleamine 2,3-dioxygenase has been detected in and/or purified from rabbit small intestine (1–7), rabbit brain (8), rat intestine (9), and rat brain (10–11). Serotonin, melatonin, D- and L-5-hydroxytryptophan, tryptamine, and D- and L-tryptophan have been shown to be substrates for indoleamine 2,3-dioxygenase. An unusual characteristic of this enzyme is the requirement for methylene blue and ascorbate in eliciting catalytic activity in vitro (1,2,5), although a recent report suggests that tetrahydrobiopterin can also serve in this process(12). Hirata and Hayaishi (3,5) have implicated the involvement of O 2 - in the reaction catalyzed by indoleamine 2,3-dioxygenase, based mainly on the ability of superoxide dismutase to inhibit the ongoing reaction. Based on my previous work with L-tryptophan 2,3-dioxygenases (13, 14), we became interested in the possibility that indoleamine 2,3-dioxygenase might also be a heme and copper containing enzyme.
KeywordsMethylene Blue Copper Content Atomic Absorption Spectroscopy Visible Absorption Spectrum Rabbit Brain
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- 8.Hirata, F., Hayaishi, O., Tokuyama, T., and Senoh, S. (1971) J. Biol. Chem., 249, 1311–1313.Google Scholar
- 13.Feigelson, P., and Brady, F.O., in Molecular Mechanisms of Oxygen Activation (O. Hayaishi, Ed.), Academic Press, New York, 1974, pp. 87–133.Google Scholar
- 14.Brady, F.O. (1976) Bioinorganic Chem., 5, in press.Google Scholar
- 17.Falk, J.E., Porphyrins and Metalloporphyrins, American Elsevier, New York, 1964, pp. 181–182, 240–241.Google Scholar
- 22.Diehl, H., and Smith, G.F. in The Copper Reagents: Cuproine, Neocuproine, Bathocuproine, G.F. Smith Chemical Co., Columbus, Ohio, 1958, pp. 39–44.Google Scholar