Tryptophan metabolism along the kynurenine pathway in diet-induced and genetic hypercholesterolemic rabbits.

Background: The activity of nicotinic acid in hypercholesterolemia has been poorly understood. In man, nicotinic acid derives for the most part from tryptophan along the tryptophan-nicotinic acid pathway, also called the kynurenine pathway, kynurenine being the key metabolite in this process. In the present paper, we investigated if, in animals with hypercolesterolemia, degradation of tryptophan to nicotinic acid along the kynurenine pathway was perturbated.

Tryptophan metabolism in rabbits.

Enzyme activities involved in tryptophan metabolism along the kynurenine pathway were studied in male New Zealand white rabbits. Activities are expressed both as specific activity and per g of fresh tissue. Liver tryptophan 2,3-dioxygenase activity (TDO), when assayed in either the absence (holoenzyme) or presence of added haematin (apoenzyme), did not change.

Kynurenine pathway enzymes in guinea pigs.

In some animals, the administration of repeated doses of tryptophan can cause death. It has been reported that guinea pig does not survive repeated doses of tryptophan, due to the absence of the hormonal induction mechanism of liver tryptophan 2,3-dioxygenase (TDO). Therefore, it was of interest to investigate if guinea pig is an animal model suitable for studying tryptophan metabolism.

Kynurenine pathway enzymes in different species of animals.

Kynurenine pathway enzyme activities, liver tryptophan 2,3-dioxygenase (TDO), small intestine indole 2,3-dioxygenase (IDO), liver and kidney kynurenine 3-monooxygenase, kynurenine-oxoglutarate transaminase, kynureninase, 3-hydroxyanthranilate 3,4-dioxygenase and aminocarboxymuconate-semialdehyde decarboxylase, were assayed in rabbits, rats, mice and guinea pigs. Their activities varied among species. Especially, TDO was present as both holoenzyme and apoenzyme only in rat, while the other species, rabbit, mouse and guinea pig, only showed holoenzyme activity.

The kynurenine pathway enzymes in healthy and hyperlipidemic rabbits.

Tryptophan metabolism along the kynurenine pathway in normolipidemic and diet-induced hyperlipidemic New Zealand rabbits was studied. The activities of liver tryptophan 2,3-dioxygenase small intestine indole 2,3-dioxygenase, liver and kidney kynurenine 3-monooxygenase, kynurenine-oxoglutarate transaminase, kynureninase, 3-hydroxyanthranilate 3,4-dioxygenase and aminocarboxymuconate semialdehyde decarboxylase (picolinic carboxylase) were determined. Liver tryptophan 2,3-dioxygenase (TDO) was present only as a holoenzyme.

Enzyme activities of tryptophan metabolism along the kynurenine pathway in various species of animals.

The purpose of this study was to investigate variations in the enzyme activities of the kynurenine pathway in various mammals (rabbit, mouse, rat, guinea-pig). 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 were analysed. Small intestine superoxide dismutase activity and free and total serum tryptophan were also measured.

Enzyme activities along the tryptophan-nicotinic acid pathway in alloxan diabetic rabbits.

Recent data from our laboratory have indicated that the rabbit is a suitable animal model for the study of enzyme activities of the tryptophan-nicotinic acid pathway. We report here the pattern of tryptophan metabolism in rabbits made diabetic with alloxan treatment, and hypercholesterolemic with a high-cholesterol diet. A group of rabbits with only hypercholesterolemia was also considered.