Tryptophan metabolism along the kynurenine pathway in rats.
Enzyme activities along the kynurenine pathway, liver tryptophan 2,3-dioxygenase, small intestine indole 2,3-dioxygenase, liver and kidney kynurenine 3-monooxygenase, kynureninase, kynurenine-oxoglutarate transaminase, 3-hydroxyanthranilate 3,4-dioxygenase, and aminocarboxymuconate-semialdehyde decarboxylase, involved in the catabolism of tryptophan, were studied in male adult Wistar albino rats. Intestine superoxide dismutase and serum tryptophan were also determined. Hepatic tryptophan 2,3-dioxygenase is present both as holoenzyme and apoenzyme, but the total activity is inferior to that of intestine indole 2,3-dioxygenase which, therefore, actively oxidizes tryptophan in rats. However, this activity is inhibited by scavengers for the superoxide anion, such as superoxide dismutase, which also shows to be active in small intestine of rat. However, the more active enzymes appeared to be kynurenine 3-monooxygenase and 3-hydroxyanthranilate 3,4-dioxygenase. The former is equally active in both liver and kidney, the latter is more active in liver. Kynurenine-oxoglutarate transaminase is much more active in kidney than in liver, and much more active than kynureninase, which shows similar activities in both tissues. In contrast to the high activity of 3-hydroxyanthranilate 3,4-dioxygenase, aminocarboxymuconate-semialdehyde decarboxylase is 30-35 times less active, showing the efficiency of conversion of tryptophan to NAD. These data demonstrate that rat is a useful animal model for studying tryptophan metabolism along the kynurenine pathway. Serum tryptophan appeared to be 90% bound to proteins. Results demonstrate that, in rat, tryptophan is mainly metabolised along the kynurenine pathway. Therefore, rat is a suitable animal model for studying tryptophan metabolism in the pathological field.
Allegri
Graziella
G
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, I-35131 Padova, Italy. graziella.allegri@unipd.it
Ragazzi
Eugenio
E
Bertazzo
Antonella
A
Costa
Carlo V L
CV
Rocchi
Raniero
R
D000818:Animals; D007421:Intestine, Small / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D007737:Kynurenine / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D013482:Superoxide Dismutase