Formation of thiazolidine-4-carboxylic acid represents a main metabolic pathway of 5-hydroxytryptamine in rat brain.
Incubation of 5-hydroxytryptamine (5-HT) with rat brain homogenate resulted in the formation of (4R)-2-[3'-(5'-hydroxyindolyl)-methyl]-1,3-thiazolidine-4-carboxyl ic acid (5'-HITCA) as the major metabolite. The substance represents the condensation product of 5-hydroxyindole-3-acetaldehyde with L-cysteine. The chemical structure was confirmed by chromatographic and chemical methods as well as by fast atom bombardment mass spectrometry. Incubation of 5-HT in the presence of L-cysteine yielded the thiazolidine as the main metabolite up to 4 h. Under these conditions, the concentration of 5-hydroxyindole-3-acetic acid (5-HIAA) amounted to about 20% and 57% of 5'-HITCA (0.5 h and 4 h, respectively). In contrast to these findings, indole-3-acetic acid (IAA) was identified as the major metabolite when tryptamine was incubated under similar conditions. (4R)-2-(3'-Indolylmethyl)-1,3-thiazolidine-4-carboxylic acid (ITCA) was found to be the main conversion product of tryptamine only during the first 30 min. To investigate the fate of the thiazolidines, radiolabelled and unlabelled ITCA was incubated with rat brain homogenate. The compound was degraded enzymatically and rapidly. Subcellular fractionation revealed that the enzyme activity was present mainly in the cytosolic fraction whereas the preparation of mitochondria showed less activity. The responsible enzyme is presumably a carbon-sulfur lyase (EC 4.4.1.-). The major metabolite was isolated by HPLC and identified by mass spectrometry as well as by comparison with reference compounds to be IAA.(ABSTRACT TRUNCATED AT 250 WORDS)
Susilo
R
R
Institut für Neuropsychopharmakologie, Freie Universität Berlin, F.R.G.
Rommelspacher
H
H
Höfle
G
G
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007210:Indoleacetic Acids / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013844:Thiazoles / Q000096:biosynthesis* / Q000378:metabolism; D053778:Thiazolidines; D013997:Time Factors; D014363:Tryptamines / Q000378:metabolism
D007210:Indoleacetic Acids; D007211:Indoles; D013844:Thiazoles; D053778:Thiazolidines; D014363:Tryptamines; C059686:2-(3'indolylmethyl)-1,3-thiazolidine-4-carboxylic acid; C059687:2-(3'-(5'-hydroxyindolyl)methyl)-1,3-thiazolidine-4-carboxylic acid; D012701:Serotonin; C030820:tryptamine; D006897:Hydroxyindoleacetic Acid; C003438:thiazolidine-4-carboxylic acid