5-Hydroxytryptamine degradation

This condition is cansed by a deficiency of one or more of the monoamine nenrotransmitters in the brain (e.g. noradrenaline, dopamine, 5-hydroxytryptamine). One means of increasing the concentration of the neurotransmitters is to inhibit one of the enzymes that degrade the neurotransmitter in the brain. For the monoamines, a key degradative enzyme is monoamine oxidase, which catalyses the reaction... 

Tryptophan appears to be converted to a larger number of metabolites than any of the other amino acids. The degradation of tryptophan in animals occurs mainly in two pathways, I and II (Figure 4.1). The first major pathway (I), initiated by the action of tryptophan dioxygenase, involves oxidation of tryptophan to N - fc > r my I ky n urenine and the formation of a series of intermediates and byproducts, most of which appear in varying amounts in the urine, the sum of which accounts for the total metabolism of tryptophan, approximately. The second pathway (II) involves hydroxylation of tryptophan to 5-hydroxytryptophan and decarboxylation of this compound to 5-hydroxytryptamine (serotonin), a potent vasoconstrictor found particularly in the brain, intestinal tissues, blood platelets, and mast cells. A small percentage (3%) of dietary tryptophan is metabolized via the pathway (III) to indoleacetic acid. Other minor pathways also exist in animal tissues. 

Viani and Horman (1976) found indole on roasting serotonin (hydroxytryptamine, 2-aminoethyI-I//-indol-5-ol), present as an amide in the waxes surrounding the coffee bean and which behaves like the related tryptophan. A pathway showing its formation in the thermal degradation of phenylalanine at 300 °C has been published by Kato et al. (1971). 

Serotonin S-hydroxytryptamine, M, 176.2, a plant and animal hormone. It is produced by hydroxylation of L-tryptophan to 5-hydroxytryptophan, followed by decarboxylation. The synthesis occurs in the central nervous system, lung, spleen and argentaffine light cells of the intestinal mucosa. S. is stored in thrombocytes and mast cells of the blood. It acts as a Neuro-transmitter (see), stimulates peristalsis of the intestine, and causes a dose-dependent constriction of smooth muscle. It stimulates the release from arterial endothelium of a dilator substance which counteracts its primary constricting effect [T.M. Cocks X A. Angus Nature 305 (1983) 627-630]. S. is a precursor of the hormone Melatonin (see). It is inactivated and degraded by monoamine oxidases and aldehyde oxidases to 5-hydroxy-indoleacetic acid. 

Hydroxyindoleacetic acid. This acid (5-HIA) is the degradation product of serotonine (5-hydroxytryptamine). Urinary elimination of over 15 mg per day renders probable the diagnosis of a metastasising carcinoid, provided the influence of diet (bananas, walnuts etc.) is excluded. Standard amounts of 5-HIA and increasing amounts of the urine extract are applied to the adsorbent in the semi-quantitative determination of Schmid and Kuschke [143]. After the TLC-separation, the plate is sprayed, with 0.1% 2,6-dichloroqiiinonechloroiniide solution in methanol and the spot sizes compared in the approximate evaluation. Especially distinct, brownish-red spots are obtained by spraying with diazotised p-nitroaniline (Fig. 173). This reaction also can be adapted to quantitative determination [143 a]. 

Tryptophan has also assumed medical importance as a result of the pharmacological action of serotonin, 5-hydroxytryptamine, and the possibility that the aromatic amines resulting from the degradation of tryptophan might be carcinogens (875). 

Functional end products of the essential amino acid tryptophan arise mainly through two distinctive pathways. The major pathway is degradation of tryptophan by oxidation, which fuels the kynurenine pathway (See 02011). The second and quantitatively minor pathway is hydroxylation of tryptophan and its subsequent decarboxylation to the indoleamine 5-hydroxytryptamine (serotonin) and subsequently melatonin. The metabolites of the kynurenine pathway, indicated as kynurenines, include quinolic acid and kynurenic acid. Quinolinic acid is an agonist of the NMDA receptor (see also section on glutamic acid), while kynurenic acid is a nonselective NMDA-receptor antagonist with a high affinity for the glycine site of the NMDA receptor (see also section on... 

Tryptophan is metabolized by several different pathways (Fig. 1) each yielding biologically important substances such as tryptamine and in particular serotonin (5-hydroxytryptamine), which seems to be involved in certain mental disorders. Indole-3-acetic acid is a plant growth hormone its precursor is tryptamine or indole-3-pyruvic acid. In humans, the microorganisms of the large intestine can further degrade indole-3-acetic acid to yield indole, skatole (3-methyl-indole) and other substances. 

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