5-Hydroxytryptophan CAS NO.56-69-9

Inhibition of allergic inflammation by supplementation with 5-hydroxytryptophan[Pubmed: 22842218]

Am J Physiol Lung Cell Mol Physiol. 2012 Oct 15; 303(8): L642–L660.

Clinical reports indicate that patients with allergy/asthma commonly have associated symptoms of anxiety/depression. Anxiety/depression can be reduced by 5-Hydroxytryptophan (5-HTP) supplementation. However, it is not known whether 5-HTP reduces allergic inflammation. Therefore, we determined whether 5-HTP supplementation reduces allergic inflammation. We also determined whether 5-HTP decreases passage of leukocytes through the endothelial barrier by regulating endothelial cell function. For these studies, C57BL/6 mice were supplemented with 5-HTP, treated with ovalbumin fraction V (OVA), house dust mite (HDM) extract, or IL-4, and examined for allergic lung inflammation and OVA-induced airway responsiveness.
METHODS AND RESULTS:
To determine whether 5-HTP reduces leukocyte or eosinophil transendothelial migration, endothelial cells were pretreated with 5-HTP, washed and then used in an in vitro transendothelial migration assay under laminar flow. Interestingly, 5-HTP reduced allergic lung inflammation by 70–90% and reduced antigen-induced airway responsiveness without affecting body weight, blood eosinophils, cytokines, or chemokines. 5-HTP reduced allergen-induced transglutaminase 2 (TG2) expression and serotonylation (serotonin conjugation to proteins) in lung endothelial cells. Consistent with the regulation of endothelial serotonylation in vivo, in vitro pretreatment of endothelial cells with 5-HTP reduced TNF-α-induced endothelial cell serotonylation and reduced leukocyte transendothelial migration. Furthermore, eosinophil and leukocyte transendothelial migration was reduced by inhibitors of transglutaminase and by inhibition of endothelial cell serotonin synthesis, suggesting that endothelial cell serotonylation is key for leukocyte transendothelial migration.
CONCLUSIONS:
In summary, 5-HTP supplementation inhibits endothelial serotonylation, leukocyte recruitment, and allergic inflammation. These data identify novel potential targets for intervention in allergy/asthma.

Oral administration of 5-hydroxytryptophan aggravated periodontitis-induced alveolar bone loss in rats.[Pubmed: 25766472]

Arch Oral Biol. 2015 May;60(5):789-98.

5-Hydroxytryptophan (5-HTP) is the precursor of serotonin and 5-Hydroxytryptophan has been widely used as a dietary supplement to raise serotonin level. Serotonin has recently been discovered to be a novel and important player in bone metabolism. As peripheral serotonin negatively regulates bone, the regular take of 5-Hydroxytryptophan may affect the alveolar bone metabolism and therefore influence the alveolar bone loss induced by periodontitis. The aim of this study was to investigate the effect of 5-Hydroxytryptophan on alveolar bone destruction in periodontitis.
METHODS AND RESULTS:
Male Sprague-Dawley rats were randomly divided into the following four groups: (1) the control group (without ligature); (2) the 5-HTP group (5-Hydroxytryptophan at 25 mg/kg/day without ligature); (3) the L group (ligature+saline placebo); and (4) the L+5-Hydroxytryptophan group (ligature+5-Hydroxytryptophan at 25 mg/kg/day). Serum serotonin levels were determined by ELISA. The alveolar bones were evaluated with micro-computed tomography and histology. Tartrate-resistant acid phosphatase staining was used to assess osteoclastogenesis. The receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) expression in the periodontium as well as the interleukin-6 positive osteocytes were analysed immunohistochemically. 5-Hydroxytryptophan significantly increased serum serotonin levels. In rats with experimental periodontitis, 5-Hydroxytryptophan increased alveolar bone resorption and worsened the micro-structural destruction of the alveolar bone. 5-Hydroxytryptophan also stimulated osteoclastogenesis and increased RANKL/OPG ratio and the number of IL-6 positive osteocytes. However, 5-Hydroxytryptophan treatment alone did not cause alveolar bone loss in healthy rats.
CONCLUSIONS:
The present study showed that 5-Hydroxytryptophan aggravated alveolar bone loss, deteriorated alveolar bone micro-structure in the presence of periodontitis, which suggests 5-Hydroxytryptophan administration may increase the severity of periodontitis.

Male-to-female transfer of 5-hydroxytryptophan glucoside during mating in Zygaena filipendulae (Lepidoptera).[Pubmed: 24012995]

Insect Biochem Mol Biol. 2013 Nov;43(11):1037-44.

Zygaena filipendulae accumulates the cyanogenic glucosides linamarin and lotaustralin by larval sequestration from the food plant or de novo biosynthesis. We have previously demonstrated that the Z. filipendulae male transfers linamarin and lotaustralin to the female in the course of mating.
METHODS AND RESULTS:
In this study we report the additional transfer of 5-Hydroxytryptophan glucoside (5-(β-d-glucopyranosyloxy)-L-Tryptophan) from the Z. filipendulae male internal genitalia to the female spermatophore around 5 h into the mating process. 5-Hydroxytryptophan glucoside is present in the virgin male internal genitalia, and production continues during the early phase of mating. Following initiation of 5-Hydroxytryptophan glucoside transfer to the female, the amount in male internal genitalia is drastically reduced until after mating where it is slowly replenished. For unambiguous structural identification, 5-Hydroxytryptophan glucoside was chemically synthesized and used as an authentic standard.
CONCLUSIONS:
The biological function of 5-Hydroxytryptophan glucoside remains to be established, although we have indications that it may be involved in inducing the female to stay in copula and delay egg-laying to prevent re-mating of the female. To our knowledge 5-Hydroxytryptophan glucoside has not previously been reported present in animal tissues.

ACS Synth Biol. 2014 Jul 18;3(7):497-505.

Engineering bacterial phenylalanine 4-hydroxylase for microbial synthesis of human neurotransmitter precursor 5-hydroxytryptophan.[Pubmed: 24936877]

5-Hydroxytryptophan (5-HTP) is a drug that is clinically effective against depression, insomnia, obesity, chronic headaches, etc. It is only commercially produced by the extraction from the seeds of Griffonia simplicifolia because of a lack of synthetic methods.
METHODS AND RESULTS:
Here, we report the efficient microbial production of 5-Hydroxytryptophan via combinatorial protein and metabolic engineering approaches. First, we reconstituted and screened prokaryotic phenylalanine 4-hydroxylase activity in Escherichia coli. Then, sequence- and structure-based protein engineering dramatically shifted its substrate preference, allowing for efficient conversion of tryptophan to 5-Hydroxytryptophan. Importantly, E. coli endogenous tetrahydromonapterin (MH4) could be utilized as the coenzyme, when a foreign MH4 recycling mechanism was introduced. Whole-cell bioconversion allowed the high-level production of 5-Hydroxytryptophan (1.1-1.2 g/L) from tryptophan in shake flasks. On this basis, metabolic engineering efforts were further made to achieve the de novo 5-HTP biosynthesis from glucose.
CONCLUSIONS:
This work not only holds great scale-up potential but also demonstrates a strategy for expanding the native metabolism of microorganisms.