5-Hydroxytryptamine conjugation

Some women suffer from mental deprc.ssion when taking estrogen-containing oral contraceptives, and this depression could be due to another malfunction in tryptophan metabolism, leading to S-hydroxytryptamine (serotonin). Some evidence indicates that the decarboxylation of S-hydroxytrypto-phan is inhibited (in vitro) by estfogen conjugates competing with pyridoxal phosphate for the decarboxylase apoenzyme. 

Hydroxytryptamine may itself undergo conjugation. Substances closely related to it, e.g., Erspamer s enteramine I, have been reported in several cases (e.g., 179, and review 237). 

A number of routes by which 5-hydroxytryptamine may be broken down or otherwise inactivated have been established . The most important involves monoamine oxidase, which converts 5-hydroxytryptamine into 5-hydroxyindoleacetaldehyde II). Catabolism is completed by an aldehyde dehydrogenase which forms 5-hydroxyindoleacetic acid III), the principal urinary metabolite of 5-hydroxytryptamine. Like noradrenaline, 5-hydroxy-tryptamine can also be conjugated with glucuronic and sulphuric acids. 

Fic. 1. Metabolism of tryptophan to serotonin (5-hydroxytryptamine) and niacin. Fyiidoxal phosphate (PLP) dependent reactions are indicated. Reactions not shown which may result in formation of products excreted in urine include the acetylation of liymuenine and 3-hydroxykynurenine, conjugation of anthranilic acid with glycine (to form o-aminohippuric acid) and with glucuronic acid, and the dehydroxylation of kynurenic acid and xanthurenic add to quinaldic add and 8-hydroxyquinaldic add, respectively. 

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