Enzyme activities involved in tryptophan metabolism along the kynurenine pathway in rabbits.
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.
Bertazzo
A
A
Department of Pharmaceutical Sciences, University of Padua, Italy.
Ragazzi
E
E
Biasiolo
M
M
Costa
C V
CV
Allegri
G
G
D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D000818:Animals; D002262:Carboxy-Lyases / Q000032:analysis; D049308:Dioxygenases; D006867:Hydrolases / Q000032:analysis; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007422:Intestines / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology*; D007737:Kynurenine / Q000378:metabolism*; D050601:Kynurenine 3-Monooxygenase; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis; D008956:Models, Chemical; D009525:Niacin / Q000378:metabolism; D010105:Oxygenases / Q000032:analysis; D010848:Picolinic Acids / Q000378:metabolism; D011817:Rabbits; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000032:analysis
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010848:Picolinic Acids; D009525:Niacin; 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; D006867:Hydrolases; C021480:kynureninase; D002262:Carboxy-Lyases; C024396:aminocarboxymuconate-semialdehyde decarboxylase; C030614:picolinic acid