大鼠体内沿犬尿氨酸途径的色氨酸代谢

Allegri Graziella, Ragazzi Eugenio, Bertazzo Antonella, Costa Carlo V L, Rocchi Raniero

Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, I-35131 Padova, Italy.

Adv Exp Med Biol. 2003;527:481-96. doi: 10.1007/978-1-4615-0135-0_56.

Enzyme activities along the kynurenine pathway, 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, involved in the catabolism of tryptophan, were studied in male adult Wistar albino rats. Intestine superoxide dismutase and serum tryptophan were also determined. Hepatic tryptophan 2,3-dioxygenase is present both as holoenzyme and apoenzyme, but the total activity is inferior to that of intestine indole 2,3-dioxygenase which, therefore, actively oxidizes tryptophan in rats. However, this activity is inhibited by scavengers for the superoxide anion, such as superoxide dismutase, which also shows to be active in small intestine of rat. However, the more active enzymes appeared to be kynurenine 3-monooxygenase and 3-hydroxyanthranilate 3,4-dioxygenase. The former is equally active in both liver and kidney, the latter is more active in liver. Kynurenine-oxoglutarate transaminase is much more active in kidney than in liver, and much more active than kynureninase, which shows similar activities in both tissues. In contrast to the high activity of 3-hydroxyanthranilate 3,4-dioxygenase, aminocarboxymuconate-semialdehyde decarboxylase is 30-35 times less active, showing the efficiency of conversion of tryptophan to NAD. These data demonstrate that rat is a useful animal model for studying tryptophan metabolism along the kynurenine pathway. Serum tryptophan appeared to be 90% bound to proteins. Results demonstrate that, in rat, tryptophan is mainly metabolised along the kynurenine pathway. Therefore, rat is a suitable animal model for studying tryptophan metabolism in the pathological field.

在成年雄性Wistar白化大鼠中研究了色氨酸分解代谢过程中犬尿氨酸途径的酶活性，包括肝脏色氨酸2,3-双加氧酶、小肠吲哚2,3-双加氧酶、肝脏和肾脏犬尿氨酸3-单加氧酶、犬尿氨酸酶、犬尿氨酸-氧代戊二酸转氨酶、3-羟基邻氨基苯甲酸3,4-双加氧酶和氨基羧基粘康酸-半醛脱羧酶。还测定了小肠超氧化物歧化酶和血清色氨酸。肝脏色氨酸2,3-双加氧酶以全酶和脱辅基酶的形式存在，但总活性低于小肠吲哚2,3-双加氧酶，因此，小肠吲哚2,3-双加氧酶在大鼠中可积极氧化色氨酸。然而，这种活性受到超氧阴离子清除剂如超氧化物歧化酶的抑制，超氧化物歧化酶在大鼠小肠中也表现出活性。然而，活性较高的酶似乎是犬尿氨酸3-单加氧酶和3-羟基邻氨基苯甲酸3,4-双加氧酶。前者在肝脏和肾脏中的活性相同，后者在肝脏中活性更高。犬尿氨酸-氧代戊二酸转氨酶在肾脏中的活性比在肝脏中高得多，并且比犬尿氨酸酶活性高得多，犬尿氨酸酶在两种组织中的活性相似。与3-羟基邻氨基苯甲酸3,4-双加氧酶的高活性相反，氨基羧基粘康酸-半醛脱羧酶的活性低30-35倍，这表明色氨酸向NAD的转化效率。这些数据表明大鼠是研究犬尿氨酸途径色氨酸代谢的有用动物模型。血清色氨酸似乎90%与蛋白质结合。结果表明，在大鼠中，色氨酸主要沿犬尿氨酸途径代谢。因此，大鼠是研究病理领域色氨酸代谢的合适动物模型。