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Formation of Thiazolidine‐4‐Carboxylic Acid Represents a Main Metabolic Pathway of 5‐Hydroxytryptamine in Rat Brain
Author(s) -
Susilo Rudy,
Rommelspacher Hans,
Höfle Gerhard
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb07259.x
Subject(s) - tryptamine , metabolite , chemistry , thiazolidine , biochemistry , incubation , enzyme , chromatography , stereochemistry
Abstract: Incubation of 5‐hydroxytryptamine (5‐HT) with rat brain homogenate resulted in the formation of (4 R )‐2‐[3′‐(5′‐hydroxyindolyl)‐methyl]‐1,3‐thiazolidine‐4‐carboxylic 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. (4 R )‐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 carbonsulfur 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. The present results suggest the involvement of L‐cysteine in the metabolism of biogenic aldehydes by forming thiazolidine‐4‐carboxylic acids. The biological rationale of this pathway might be a control mechanism of the chemically active aldehydes by the rapid inactivation of the compounds.