Utilization of Superoxide Anion by Indoleamine Oxygenase-Catalyzed Tryptophan and Indoleamine Oxidation

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Abstract

In 1963, we isolated from rabbit intestine a new enzyme that catalyzed the formation of D-kynurenine from D-tryptophan (Higuchi et al., 1963). In contrast to the classical tryptophan dioxygenase, this enzyme exhibits broad substrate specificity and acts upon various indoleamine derivatives, including tryptophan. Therefore it was termed indoleamine 2,3-dioxygenase, abbreviated as IDO. Typtophan dioxygenase, abbreviated as TPO, is found only in the liver, and acts only on L-tryptophan. In contrast, IDO is widely distributed in various tissues and organs, except the liver. It has a broad substrate specificity, and acts upon not only L- and D-tryptophan but also 5-hydroxy-tryptophan, tryptamine, serotonin, etc, although tryptophan is a far better substrate in terms of Km and Vmax. TPO utilizes molecular oxygen, whereas IDO requires and utilizes superoxide anion and molecular oxygen for its activity. Although both IDO and TPO are hemoproteins, their molecular properties are clearly different with regard to their molecular weight, subunit structure, carbohydrate and heme contents, and the turnover number. They are also different immunologically. Thus, there are two distinctly different enzymes both catalyzing essentially identical reactions, namely the formation of formylkynurenine from tryptophan. However, unlike TPO, IDO is not induced by either tryptophan or glucocorticoid, but is induced under various pathological conditions.