Enzyme activities along the kynurenine pathway in mice.
Tryptophan metabolism was studied in adult male Swiss mice by determining enzyme activities along the kynurenine pathway. The following enzymes were assayed: 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. Liver tryptophan 2,3-dioxygenase was present only as a holoenzyme: similar results were obtained in the absence or in the presence of the cofactor haematin. The specific activity of small intestine indole 2,3-dioxygenase was higher than that of tryptophan 2,3-dioxygenase. As superoxide dismutase was very active in mouse intestine, this enzyme may be one of the rate controlling factors of the indole 2,3 dioxygenase activity. Kynurenine 3-monooxygenase appeared to be very active. Kidneys showed higher activity than liver. Instead, kynureninase was more active in liver, but activity was lower than that demonstrated by the other enzymes of the kynurenine pathway. Conversely, kynurenine-oxoglutarate transaminase was much more active in kidney than in liver. However, the most active enzyme along the kynurenine pathway was 3-hydroxyanthranilate 3,4-dioxygenase, with liver showing the highest activity; aminocarboxymuconate-semialdehyde decarboxylase, which showed similar values in both liver and kidney, showed activity markedly lower than 3-hydroxyanthranilate 3,4-dioxygenase. Serum tryptophan appeared to be 87% bound to proteins. Results demonstrate that, in mouse, tryptophan is mainly metabolised along the kynurenine pathway. Therefore, mouse 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
D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000818:Animals; D049308:Dioxygenases; D007421:Intestine, Small / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D007737:Kynurenine / Q000378:metabolism*; D050601:Kynurenine 3-Monooxygenase; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism
D007737:Kynurenine; D014364:Tryptophan; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D049308:Dioxygenases; D014366:Tryptophan Oxygenase; D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D050601:Kynurenine 3-Monooxygenase; D013482:Superoxide Dismutase