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标题：Formation of 5-hydroxykynurenine and 5-hydroxykynurenamine from 5-hydroxytryptophan in rabbit small intestine
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作者：Motokazu Fujiwara ; Masakatsu Shibata ; Yoshitsugu Nomiyama 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1979
卷号：76
期号：3
页码：1145-1149
DOI：10.1073/pnas.76.3.1145
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In order to clarify the role of indoleamine 2,3-dioxygenase [indole:oxygen 2,3-oxidoreductase (decyclizing), EC 1.13.11.17 ] in the metabolism of serotonin, DL-5-hydroxy[methylene-14C]tryptophan, a precursor of serotonin, was incubated with slices of rabbit ileum. Resulting metabolites were separated by DEAE-cellulose column and polyamide column chromatography and identified by various chromatographic techniques and enzymatic analysis. Metabolites obtained in significant amounts were serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-hydroxykynurenine, 5-hydroxykynurenamine, and 4,6-dihydroxyquinoline, representing 13.2, 15.8, 7.0, 21.9, 1.3, and 2.6% of the total metabolites, respectively. The first three compounds were previously reported to be major metabolites produced from 5-hydroxytryptophan by the action of aromatic L-amino acid decarboxylase and monoamine oxidase, whereas the last three are formed by the cleavage of the indole ring by the action of indoleamine 2,3-dioxygenase. In the presence of pargyline, a monoamine oxidase inhibitor, the major metabolites obtained were serotonin, 5-hydroxykynurenine, and 5-hydroxykynurenamine, representing 29.6, 26.6, and 5.4% of the total metabolites, respectively. In the presence of RO4-4602, an aromatic amino acid decarboxylase inhibitor, 5-hydroxykynurenine was the sole major product. These results strongly suggest that the newly discovered metabolic pathway involving the cleavage of the indole ring of 5-hydroxytryptophan operates in vivo to a significant extent and that indoleamine 2,3-dioxygenase plays an important role in the regulation of serotonin levels in the small intestine of the rabbit.
关键词：indoleamine 2,3-dioxygenase ; indole ring cleavage ; serotonin