Biochemistry of Amino Acids - A. Master 1961

Intermediary Metabolism of Amino Acids
Tryptophan
5-Hydroxytryptophan and Its Metabolic Products

One of the Major Metabolic Pathways of Tryptophan in animal organisms is its conversion into 5-hydroxytryptamine. Years have passed since Werle and Mennicken [836] reported that tryptophan is converted in mammalian Tissues into a substance exhibiting pressor activity; the authors considered this substance to be tryptamine. Recent studies by Udenfriend and co-workers [837, 838] have demonstrated that this compound is, in all probability, 5-hydroxytryptamine. It is identical with the invertebrate hormone enteramine [839], or serotonin [840–842]. Tryptophan serves as the precursor of 5-hydroxytryptamine, as proven by experiments in which labeled 5-hydroxytryptamine was isolated after feeding labeled tryptophan to rabbits and toads [843]. 5-Hydroxytryptamine is formed via the following reactions:

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It is suggested that this transformation involves initial oxidation of the aromatic ring followed by decarboxylation of the side chain, since under the same conditions tryptamine is neither formed nor converted into 5-hydroxytryptamine. Isotope experiments utilizing the trapping method have demonstrated the Conversion of Tryptophan into 5-hydroxytryptamine by guinea pig and rat Liver slices [844]. Following the administration of 5-hydroxytryptophan, dogs excrete 5-hydroxytryptamine [844].

The enzyme catalyzing reaction (2), 5-hydroxytryptophan decarboxylase, has been found in certain animal tissues and isolated in purified form from pig and guinea pig Kidneys [838]. The enzyme is a Pyridoxal phosphate protein [1129]; it is inactive toward 3,4-dihydroxyphenylalanine, 7-hydroxytryptophan, tryptophan, and the D-isomer of 5-hydroxytryptophan. 5-Hydroxytryptamine exhibits diverse pharmacological effects, displaying pressor, depressor, and antidiuretic activity. Chromaffin tumors secrete large amounts of 5-hydroxytryptamine (p. 479).

The conversion of 5-hydroxytryptamine into 5-hydroxyindoleacetic acid has been observed in dogs [844]. The latter is also a normal constituent of human urine [845, 846], being excreted partly as a conjugate with Glycine (5-hydroxyindoleacetylglycine) [847, 848].

5-Hydroxyindoleacetic acid is presumably formed through the action of monoamine oxidase; evidence also points to The intermediate formation of 5-hydroxyindoleacetaldehyde [843].

The tryptophan peroxidase system is inactive toward 5-hydroxytryptophan; this amino acid is not utilized by a tryptophan-adapted strain of Pseudomonas [799, 849]. However, Chromobacterium violaceum converts tryptophan into 5-hydroxytryptophan [850]. It has been suggested [851] that 5-hydroxytryptophan acts as a precursor of the pigment violacein synthesized by this microorganism, which apparently lacks the kynurenine pathway of tryptophan degradation.

Toads [852, 853], certain invertebrates [854], and some plants [855, 856] contain N-dimethyl-5-hydroxytryptamine (bufotenine), which is presumably formed by the methylation of 5-hydroxytryptamine. In addition, several related compounds have been isolated, namely bufotenidine [858, 859], dehydrobufotenine [860], and bufothionine [861]. These are likewise believed to be derived from 5-hydroxytryptamine.