Indole peroxygenase activity of indoleamine 2,3-dioxygenase.
The heme enzyme indoleamine 2,3-dioxygenase (IDO) was found to catalyze the oxidation of indole by H(2)O(2), with generation of 2- and 3-oxoindole as the major products. This reaction occurred in the absence of O(2) and reducing agents and was not inhibited by superoxide dismutase or hydroxyl radical scavengers, although it was strongly inhibited by L-Trp. The stoichiometry of the reaction indicated a one-to-one correspondence for the consumption of indole and H(2)O(2). The (18)O-labeling experiments indicated that the oxygen incorporated into the monooxygenated products was derived almost exclusively from H(2)(18)O(2), suggesting that electron transfer was coupled to the transfer of oxygen from a ferryl intermediate of IDO. These results demonstrate that IDO oxidizes indole by means of a previously unrecognized peroxygenase activity. We conclude that IDO inserts oxygen into indole in a reaction that is mechanistically analogous to the "peroxide shunt" pathway of cytochrome P450.
Department of Biochemistry and Molecular Biology, Life Sciences Centre, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
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D000818:Animals; D001234:Aspergillus niger / Q000201:enzymology; D000077463:Carbamide Peroxide; D002417:Cattle; D004926:Escherichia coli / Q000201:enzymology; D004950:Esterases / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D005949:Glucose Oxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000737:chemistry / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010103:Oxygen Isotopes; D010545:Peroxides / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013552:Swine; D014364:Tryptophan / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives / Q000378:metabolism
D016166:Free Radical Scavengers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D010103:Oxygen Isotopes; D010545:Peroxides; D000077463:Carbamide Peroxide; C030374:indole; D014364:Tryptophan; D014508:Urea; D006861:Hydrogen Peroxide; D006899:Mixed Function Oxygenases; D005949:Glucose Oxidase; C022333:peroxygenase; D013482:Superoxide Dismutase; D004950:Esterases