Properties and function of indoleamine 2,3-dioxygenase.
Available evidence indicates that indoleamine 2,3-dioxygenase, which is particularly abundant in the lung, colon, and intestine, catalyzes the oxidative ring cleavage of the pyrrole moiety of not only tryptophan and 5-hydroxytryptophan but also serotonin, melatonin, and other indoleamine derivatives. Our recent experiments with slices of intestine, together with those with organ culture of pineal glands, perfusion of heart and lung preparations and intact animals, which I did not have time to mention today, indicate that the oxygenative ring cleavages of various indoleamines do occur in vivo to a significant extent. Secondly, this enzyme appears to utilize superoxide anion rather than molecular oxygen. If superoxide anion is demonstrated, unequivocally, to be the true substrate of this enzyme, not only in vitro but also in vivo, then indoleamine 2,3-dioxygenase may be the first example of a new class of enzymes which utilize superoxide anion as an oxidizing agent just as peroxidases utilize hydrogen peroxide. Lastly, this novel enzyme produced a new class of biogenic amines, which may be referred to, generically, as "anthraniloylamines." Although their natural occurrence has not yet been established, they may have hitherto unknown biological or pharmacological activities and are currently under investigation in our laboratory.
D001545:Benserazide / Q000494:pharmacology; D001665:Binding Sites; D005609:Free Radicals; D007421:Intestine, Small / Q000201:enzymology; D007700:Kinetics; D007735:Kynuramine / Q000031:analogs & derivatives / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009928:Organ Specificity; D010100:Oxygen; D010105:Oxygenases / Q000302:isolation & purification / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011485:Protein Binding; D012701:Serotonin / Q000494:pharmacology; D013053:Spectrophotometry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000494:pharmacology
D005609:Free Radicals; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D007735:Kynuramine; D001545:Benserazide; D010105:Oxygenases; D013482:Superoxide Dismutase; D010100:Oxygen