Enzyme activities involved in tryptophan metabolism along the kynurenine pathway in rabbits

Biochim Biophys Acta. 2001 Aug 15;1527(3):167-75. doi: 10.1016/s0304-4165(01)00165-9.

Abstract

The following enzyme activities of the tryptophan-nicotinic acid pathway were studied in male New Zealand rabbits: liver tryptophan 2,3-dioxygenase, intestine indole 2,3-dioxygenase, liver and kidney kynurenine 3-monooxygenase, kynureninase, kynurenine-oxoglutarate transaminase, 3-hydroxyanthranilate 3,4-dioxygenase, and aminocarboxymuconate-semialdehyde decarboxylase. Intestine superoxide dismutase and serum tryptophan were also determined. Liver tryptophan 2,3-dioxygenase exists only as holoenzyme, but intestine indole 2,3-dioxygenase is very active and can be considered the key enzyme which determines how much tryptophan enters the kynurenine pathway also under physiological conditions. The elevated activity of indole 2,3-dioxygenase in the rabbit intestine could be related to the low activity of superoxide dismutase found in intestine. Kynurenine 3-monooxygenase appeared more active than kynurenine-oxoglutarate transaminase and kynureninase, suggesting that perhaps a major portion of kynurenine available from tryptophan may be metabolized to give 3-hydroxyanthranilic acid, the precursor of nicotinic acid. In fact, 3-hydroxyanthranilate 3,4-dioxygenase is much more active than the other previous enzymes of the kynurenine pathway. In the rabbit liver 3-hydroxyanthranilate 3,4-dioxygenase and aminocarboxymuconate-semialdehyde decarboxylase show similar activities, but in the kidney 3-hydroxyanthranilate 3,4-dioxygenase activity is almost double. These data suggest that in rabbit tryptophan is mainly metabolized along the kynurenine pathway. Therefore, the rabbit can also be a suitable model for studying tryptophan metabolism in pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyanthranilate 3,4-Dioxygenase
  • Animals
  • Carboxy-Lyases / analysis
  • Dioxygenases*
  • Hydrolases / analysis
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Intestines / enzymology*
  • Kidney / enzymology*
  • Kynurenine / metabolism*
  • Kynurenine 3-Monooxygenase
  • Liver / enzymology*
  • Male
  • Mixed Function Oxygenases / analysis
  • Models, Chemical
  • Niacin / metabolism
  • Oxygenases / analysis
  • Picolinic Acids / metabolism
  • Rabbits
  • Tryptophan / blood
  • Tryptophan / metabolism*
  • Tryptophan Oxygenase / analysis

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Picolinic Acids
  • Niacin
  • Kynurenine
  • Tryptophan
  • Mixed Function Oxygenases
  • Oxygenases
  • Dioxygenases
  • Tryptophan Oxygenase
  • 3-Hydroxyanthranilate 3,4-Dioxygenase
  • Kynurenine 3-Monooxygenase
  • Hydrolases
  • kynureninase
  • Carboxy-Lyases
  • aminocarboxymuconate-semialdehyde decarboxylase
  • picolinic acid