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

The following enzyme activities of the tryptophan-nicotinic acid pathway we re studied in male New Zealand rabbits: liver tryptophan 2,3-dioxygenase, i ntestine indole 2,3-dioxygenase, liver and kidney kynurenine 3-monooxygenas e, kynureninase, kynurenine-oxoglutarate transaminase, 3-hydroxyanthranilat e 3,4-dioxygenase, and aminocarboxymuconate-semialdehyde decarboxylase. Int estine superoxide dismutase and serum tryptophan were also determined. Live r tryptophan 2,3-dioxygenase exists only as holoenzyme, but intestine indol e 2,3-dioxygenase is very active and can be considered the key enzyme which determines how much tryptophan enters the kynurenine pathway also under ph ysiological conditions. The elevated activity of indole 2,3-dioxygenase in the rabbit intestine could be related to the low activity of superoxide dis mutase 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 met abolized to give 3-hydroxyanthranilic acid, the precursor of nicotinic acid . In fact, 3-hydroxyanthranilate 3,4-dioxygenase is much more active than t he other previous enzymes of the kynurenine pathway. In the rabbit liver 3- hydroxyanthranilate 3,4-dioxygenase and aminocarboxymuconate-semialdehyde d ecarboxylase show similar activities, but in the kidney 3-hydroxyanthranila te 3,4-dioxygenase activity is almost double. These data suggest that in ra bbit tryptophan is mainly metabolized along the kynurenine pathway. Therefo re, the rabbit can also be a suitable model for studying tryptophan metabol ism in pathological conditions. (C) 2001 Elsevier Science B.V. All rights r eserved.