Pseudomonad and Hepatic L-Tryptophan 2, 3-Dioxygenase

Abstract

Kotake and collaborators discovered the ability of liver preparations to convert L-tryptophan to L-kynurenine (1). Knox and Mehler found that this overall reaction was the resultant of the activities of two distinct enzymes the first of which was tryptophan oxygenase which catalyzed the conversion of L-tryptophan to L-formylkynurenine (2). A similar enzyme was identified by Hayaishi and Stanier within extracts of Pseudomonas grown in L-tryptophan (3). Tanaka and Knox found this enzyme to be a heme protein (4). Subsequently Feigelson and Greengard prepared the apoenzyme and demonstrated restoration of tryptophan oxygenase catalytic activity by the addition of heme (ferriprotoporphyrin IX) thus confirming the catalytically essential role of heme in the functioning of this enzyme (5). We have since purified tryptophan oxygenase to homogeneity from both rat liver and induced Pseudomonas (6, 7). Our laboratory also demonstrated the presence of two moles of copper and two moles of heme per tetremer of enzyme and have produced other evidence suggesting a catalyic function for the copper as well as the heme moiety (8, 9, 10).