Serotonin catabolism and the formation and fate of 5-hydroxyindole thiazolidine carboxylic Acid.
Serotonin (5-HT) functions as a neurotransmitter and neuromodulator in both the central and enteric nervous systems of mammals. The dynamic degradation of 5-HT metabolites in 5-HT-containing nervous system tissues is monitored by capillary electrophoresis with wavelength-resolved laser-induced native fluorescence detection in an effort to investigate known and novel 5-HT catabolic pathways. Tissue samples from wild type mice, genetically altered mice, Long Evans rats, and cultured differentiated rat pheochromocytoma PC-12 cells, are analyzed before and after incubation with excess 5-HT. From these experiments, several new compounds are detected. One metabolite, identified as 5-hydroxyindole thiazoladine carboxylic acid (5-HITCA), has been selected for further study. In 5-HT-incubated central and enteric nervous system tissue samples and differentiated PC-12 cells, 5-HITCA forms at levels equivalent to 5-hydroxyindole acetic acid, via a condensation reaction between l-cysteine and 5-hydroxyindole acetaldehyde. In the enteric nervous system, 5-HITCA is detected without the addition of 5-HT. The levels of l-cysteine and homocysteine in rat brain mitochondria are measured between 80 and 140 mum and 1.9 and 3.4 mum, respectively, demonstrating that 5-HITCA can be formed using available, free l-cysteine in these tissues. The lack of significant accumulation of 5-HITCA in the central and enteric nervous systems, along with data showing the degradation of 5-HITCA into 5-hydroxyindole acetaldehyde, suggests that an equilibrium coupled to the enzyme, aldehyde dehydrogenase type 2, prevents the accumulation of 5-HITCA. Even so, the formation of 5-HITCA represents a catabolic pathway of 5-HT that can affect the levels of 5-HT-derived compounds in the body.[1]References
- Serotonin catabolism and the formation and fate of 5-hydroxyindole thiazolidine carboxylic Acid. Squires, L.N., Jakubowski, J.A., Stuart, J.N., Rubakhin, S.S., Hatcher, N.G., Kim, W.S., Chen, K., Shih, J.C., Seif, I., Sweedler, J.V. J. Biol. Chem. (2006) [Pubmed]
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