In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 76, No. 3 ( 1979-03), p. 1145-1149
Abstract:
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 - 14 C]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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.76.3.1145
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1979
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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