Enzyme activities Along the kynurenine pathway in mice

  • Allegri Graziella
  • Eugenio Ragazzi
  • Bertazzo Antonella
  • Carlo V. L. Costa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 527)

Abstract

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 aminocarboxymuconatesemialdehyde 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 3hydroxyanthranilate 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.

Keywords

Superoxide Influenza Hydrocortisone Serotonin Interferon 

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Allegri Graziella
    • 1
  • Eugenio Ragazzi
    • 2
  • Bertazzo Antonella
    • 1
  • Carlo V. L. Costa
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversity of PadovaPadovaItaly
  2. 2.Department of Pharmacology and AnaesthesiologyUniversity of PadovaPadovaItaly

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