Tryptophan

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"Tryptan" redirects here. For the type of anti-migraine drug, see Triptan. For the hydrocarbon, see Triptane.

l-Tryptophan

Skeletal formula of L-tryptophan
Names
IUPAC name
Tryptophan
Systematic IUPAC name
(2S)-2-amino-3-(1H-indol-3-yl)propanoic acid
Other names
2-Amino-3-(1H-indol-3-yl)propanoic acid
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.000.723 Edit this at Wikidata
IUPHAR/BPS
KEGG
UNII
  • InChI=1S/C11H12N2O2/c12-9(11(14)15)5-7-6-13-10-4-2-1-3-8(7)10/h1-4,6,9,13H,5,12H2,(H,14,15)/t9-/m0/s1 checkY
    Key: QIVBCDIJIAJPQS-VIFPVBQESA-N checkY
  • c1[nH]c2ccccc2c1C[C@H](N)C(=O)O
  • Zwitterion: c1[nH]c2ccccc2c1C[C@H]([NH3+])C(=O)[O-]
Properties
C11H12N2O2
Molar mass 204.229 g·mol−1
Soluble: 0.23 g/L at 0 °C,

11.4 g/L at 25 °C,
17.1 g/L at 50 °C,
27.95 g/L at 75 °C

Solubility Soluble in hot alcohol, alkali hydroxides; insoluble in chloroform.
Acidity (pKa) 2.38 (carboxyl), 9.39 (amino)[2]
-132.0·10−6 cm3/mol
Pharmacology
N06AX02 (WHO)
Supplementary data page
Tryptophan (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Tryptophan (symbol Trp or W)[3] is an α-

codon
UGG.

Like other amino acids, tryptophan is a

protonated (–NH+
3; pKa = 9.39) and the carboxylic acid is deprotonated ( –COO−; pKa = 2.38).[5]

Humans and many animals cannot synthesize tryptophan: they need to obtain it through their diet, making it an

interstellar gas of the star cluster IC 348.[6]

Tryptophan is named after the digestive enzymes

one-letter symbol W based on the double ring being visually suggestive to the bulky letter.[8]

Function

Metabolism of l-tryptophan into serotonin and melatonin (left) and niacin (right). Transformed functional groups after each chemical reaction are highlighted in red.

Amino acids, including tryptophan, are used as building blocks in

compounds
:

The disorder fructose malabsorption causes improper absorption of tryptophan in the intestine, reduced levels of tryptophan in the blood,[16] and depression.[17]

In bacteria that synthesize tryptophan, high cellular levels of this amino acid activate a

transcription of downstream DNA that codes for the enzymes involved in the biosynthesis of tryptophan. So high levels of tryptophan prevent tryptophan synthesis through a negative feedback loop, and when the cell's tryptophan levels go down again, transcription from the trp operon
resumes. This permits tightly regulated and rapid responses to changes in the cell's internal and external tryptophan levels.

Tryptophan metabolism by
human gastrointestinal microbiota (
)
Tryptophanase-
expressing
bacteria
AST-120
Intestinal
immune
cells
Mucosal homeostasis:
↓
TNF-α
↑Junction protein-
coding mRNAs
β-amyloid
fibril formation
Maintains mucosal reactivity:
↑IL-22 production
Associated with
calcification
Associated with
Uremic toxin
The image above contains clickable links
This diagram shows the biosynthesis of
activated charcoal), an intestinal sorbent that is taken by mouth, adsorbs indole, in turn decreasing the concentration of indoxyl sulfate in blood plasma.[19]

Recommended dietary allowance

In 2002, the

Recommended Dietary Allowance (RDA) of 5 mg/kg body weight/day of tryptophan for adults 19 years and over.[23]

Dietary sources

Tryptophan is present in most protein-based foods or dietary proteins. It is particularly plentiful in

pumpkin seeds, hemp seeds, buckwheat, spirulina, and peanuts. Contrary to the popular belief[24][25] that cooked turkey contains an abundance of tryptophan, the tryptophan content in turkey is typical of poultry.[26]

Tryptophan (Trp) content of various foods[26][27]
Food Tryptophan
[g/100 g of food] 		Protein
[g/100 g of food] 		Tryptophan/protein
[%]
Egg white, dried 1.00 81.10 1.23
Spirulina, dried 0.92 57.47 1.62
Cod, Atlantic, dried 0.70 62.82 1.11
Soybeans
, raw		 0.59 36.49 1.62
Cheese,
Parmesan
 0.56 37.90 1.47
Chia seeds, dried 0.44 16.50 2.64
Sesame seed
 0.37 17.00 2.17
Hemp seed, hulled 0.37 31.56 1.17
Cheese, Cheddar 0.32 24.90 1.29
Sunflower seed 0.30 17.20 1.74
Pork, chop 0.25 19.27 1.27
Turkey 0.24 21.89 1.11
Chicken
 0.24 20.85 1.14
Beef 0.23 20.13 1.12
Oats 0.23 16.89 1.39
Salmon 0.22 19.84 1.12
Lamb, chop 0.21 18.33 1.17
Perch, Atlantic 0.21 18.62 1.12
Chickpeas, raw 0.19 19.30 0.96
Egg
 0.17 12.58 1.33
Wheat flour, white 0.13 10.33 1.23
Baking chocolate, unsweetened 0.13 12.90 1.23
Milk 0.08 3.22 2.34
Rice, white, medium-grain, cooked 0.03 2.38 1.18
Quinoa, uncooked 0.17 14.12 1.20
Quinoa, cooked 0.05 4.40 1.10
Potatoes, russet 0.02 2.14 0.84
Tamarind 0.02 2.80 0.64
Banana 0.01 1.03 0.87

Medical use

Depression

Because tryptophan is converted into

major depression. There is evidence that blood tryptophan levels are unlikely to be altered by changing the diet,[28][29] but consuming purified tryptophan increases the serotonin level in the brain, whereas eating foods containing tryptophan does not.[30]

In 2001 a

Cochrane review of the effect of 5-HTP and tryptophan on depression was published. The authors included only studies of a high rigor and included both 5-HTP and tryptophan in their review because of the limited data on either. Of 108 studies of 5-HTP and tryptophan on depression published between 1966 and 2000, only two met the authors' quality standards for inclusion, totaling 64 study participants. The substances were more effective than placebo in the two studies included but the authors state that "the evidence was of insufficient quality to be conclusive" and note that "because alternative antidepressants exist which have been proven to be effective and safe, the clinical usefulness of 5-HTP and tryptophan is limited at present".[31] The use of tryptophan as an adjunctive therapy in addition to standard treatment for mood and anxiety disorders is not supported by the scientific evidence.[31][32]

Insomnia

The

clinical practice guidelines recommended against the use of tryptophan in the treatment of insomnia due to poor effectiveness.[33]

Side effects

Potential

drowsiness, lightheadedness, headache, dry mouth, blurred vision, sedation, euphoria, and nystagmus (involuntary eye movements).[34][35]

Interactions

Tryptophan taken as a dietary supplement (such as in tablet form) has the potential to cause serotonin syndrome when combined with antidepressants of the MAOI or SSRI class or other strongly serotonergic drugs.[35] Because tryptophan supplementation has not been thoroughly studied in a clinical setting, its interactions with other drugs are not well known.[31]

Isolation

The isolation of tryptophan was first reported by

Frederick Hopkins in 1901.[36] Hopkins recovered tryptophan from hydrolysed casein, recovering 4–8 g of tryptophan from 600 g of crude casein.[37]

Biosynthesis and industrial production

As an essential amino acid, tryptophan is not synthesized from simpler substances in humans and other animals, so it needs to be present in the diet in the form of tryptophan-containing proteins. Plants and

phosphoribosylpyrophosphate (PRPP), generating pyrophosphate as a by-product. The ring of the ribose moiety is opened and subjected to reductive decarboxylation, producing indole-3-glycerol phosphate; this, in turn, is transformed into indole. In the last step, tryptophan synthase catalyzes the formation of tryptophan from indole and the amino acid serine
.

The industrial production of tryptophan is also

aromatic amino acids or multiple/overexpressed trp operons. The conversion is catalyzed by the enzyme tryptophan synthase.[39][40][41]

Society and culture

Showa Denko contamination scandal

There was a large

eosinophilia-myalgia syndrome (EMS) in the U.S. in 1989, with more than 1,500 cases reported to the CDC and at least 37 deaths.[42] After preliminary investigation revealed that the outbreak was linked to intake of tryptophan, the U.S. Food and Drug Administration (FDA) recalled tryptophan supplements in 1989 and banned most public sales in 1990,[43][44][45] with other countries following suit.[46][47]

Subsequent studies suggested that EMS was linked to specific batches of L-tryptophan supplied by a single large Japanese manufacturer,

dimer.[54]

The FDA loosened its restrictions on sales and marketing of tryptophan in February 2001,[43] but continued to limit the importation of tryptophan not intended for an exempted use until 2005.[55]

The fact that the Showa Denko facility used

genetically engineered bacteria to produce the contaminated batches of L-tryptophan later found to have caused the outbreak of eosinophilia-myalgia syndrome has been cited as evidence of a need for "close monitoring of the chemical purity of biotechnology-derived products".[56] Those calling for purity monitoring have, in turn, been criticized as anti-GMO activists who overlook possible non-GMO causes of contamination and threaten the development of biotech.[57]

Turkey meat and drowsiness hypothesis

See also: Postprandial somnolence § Turkey and tryptophan

A common assertion in the US and the UK

large neutral amino acid transporter (which transports both BCAA and aromatic amino acids), resulting in more uptake of tryptophan across the blood–brain barrier into the cerebrospinal fluid (CSF).[63][64][65] Once in the CSF, tryptophan is converted into serotonin in the raphe nuclei by the normal enzymatic pathway.[61][66] The resultant serotonin is further metabolised into the hormone melatonin—which is an important mediator of the circadian rhythm[67]—by the pineal gland.[11] Hence, these data suggest that "feast-induced drowsiness"—or postprandial somnolence—may be the result of a heavy meal rich in carbohydrates, which indirectly increases the production of melatonin in the brain, and thereby promotes sleep.[60][61][62][66]

Research

In 1912

hydroxyl group. By this reaction, tryptophan gives rise to tryptophol.[68]

Tryptophan affects brain serotonin synthesis when given orally in a purified form and is used to modify serotonin levels for research.[30] Low brain serotonin level is induced by administration of tryptophan-poor protein in a technique called acute tryptophan depletion.[69] Studies using this method have evaluated the effect of serotonin on mood and social behavior, finding that serotonin reduces aggression and increases agreeableness.[70]

Fluorescence

Main article: Fluorescence spectroscopy § Tryptophan fluorescence

Tryptophan is an important intrinsic fluorescent probe (amino acid), which can be used to estimate the nature of the microenvironment around the tryptophan residue. Most of the intrinsic fluorescence emissions of a folded protein are due to excitation of tryptophan residues.

See also

References

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    Figure 1: Molecular mechanisms of action of indole and its metabolites on host physiology and disease
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Further reading

External links

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