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Tryptophan (IUPAC-IUBMB abbreviation: Trp or W; IUPAC abbreviation: L-Trp or D-Trp; sold for medical use as Tryptan)[1] is one of the 22 standard amino acids and an essential amino acid in the human diet, as demonstrated by its growth effects on rats. It is encoded in the standard genetic code as the codon UGG. Only the L-stereoisomer of tryptophan is used in structural or enzyme proteins, but the R -stereoisomer is occasionally found in naturally produced peptides (for example, the marine venom peptide contryphan).[2] The distinguishing structural characteristic of tryptophan is that it contains an indole functional group.


The isolation of tryptophan was first reported by Frederick Hopkins in 1901[3] through hydrolysis of casein. From 600 grams of crude casein one obtains 4-8 grams of tryptophan.[4]

Biosynthesis and industrial production

Plants and microorganisms commonly synthesize tryptophan from shikimic acid or anthranilate.[5] The latter condenses with phosphoribosylpyrophosphate (PRPP), generating pyrophosphate as a by-product. After ring opening of the ribose moiety and following reductive decarboxylation, indole-3-glycerinephosphate is produced, which in turn is transformed into indole. In the last step, tryptophan synthase catalyzes the formation of tryptophan from indole and the amino acid serine.

Tryptophan biosynthesis (en).svg

The industrial production of tryptophan is also biosynthetic and is based on the fermentation of serine and indole using either wild-type or genetically modified bacteria such as B. amyloliquefaciens, B. subtilis, C. glutamicum or E. coli. These strains carry either mutations that prevent the reuptake of aromatic amino acids or multiple/overexpressed trp operons. The conversion is catalyzed by the enzyme tryptophan synthase.[6]


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

For many organisms (including humans), tryptophan is an essential amino acid. This means that it is essential for human life, cannot be synthesized by the organism, and therefore must be part of our diet. Amino acids, including tryptophan, act as building blocks in protein biosynthesis. In addition, tryptophan functions as a biochemical precursor for the following compounds (see also figure to the right):

The disorder fructose malabsorption causes improper absorption of tryptophan in the intestine, reduced levels of tryptophan in the blood[12] and depression.[13] The authors did not find reduced tryptophan in lactose maldigestion. [14]

In bacteria that synthesize tryptophan, high cellular levels of this amino acid activate a repressor protein, which binds to the trp operon.[15] Binding of this repressor to the tryptophan operon prevents 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 are reduced, transcription from the trp operon resumes. The genetic organisation of the trp operon thus permits tightly regulated and rapid responses to changes in the cell's internal and external tryptophan levels.

Dietary sources

Tryptophan is a routine constituent of most protein-based foods or dietary proteins. It is particularly plentiful in chocolate, oats, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas, sunflower seeds, pumpkin seeds, spirulina, bananas, and peanuts.[16] Despite popular belief[citation needed] that turkey has a particularly high amount of tryptophan, the amount of tryptophan in turkey is typical of most poultry.[17] There is also a myth that plant protein lacks tryptophan; in fact, tryptophan is present in significant amounts in almost all forms of plant protein, and abundant in some.

Tryptophan (Trp) Content of Various Foods[17][18]

Food Protein
[g/100 g of food]
[g/100 g of food]
Tryptophan/Protein [%]
egg, white, dried
spirulina, dried
cod, atlantic, dried
soybeans, raw
cheese, Parmesan
sesame seed
cheese, cheddar
sunflower seed
pork, chop
lamb, chop
perch, Atlantic
chickpeas, raw
wheat flour, white
baking chocolate, unsweetened
rice, white
potatoes, russet

Use as a dietary supplement and drug

There is evidence that blood tryptophan levels are unlikely to be altered by changing the diet,[19] but for some time,[vague] tryptophan has been available in health food stores as a dietary supplement.

Clinical research has shown mixed results with respect to tryptophan's effectiveness as a sleep aid, especially in normal patients.[20][21][22] Tryptophan has shown some effectiveness for treatment of a variety of other conditions typically associated with low serotonin levels in the brain.[23] In particular, tryptophan has shown some promise as an antidepressant alone[24] and as an "augmenter" of antidepressant drugs.[24][25] However, the reliability of these clinical trials has been questioned because of lack of formal controls and repeatability.[26][27][28] In addition, tryptophan itself may not be useful in the treatment of depression or other serotonin-dependent moods, but may be useful in understanding the chemical pathways that will give new research directions for pharmaceuticals.[29]


A metabolite of tryptophan, 5-hydroxytryptophan (5-HTP), has been suggested as a treatment for epilepsy[30] and depression, since 5-HTP readily crosses the blood–brain barrier and in addition is rapidly decarboxylated to serotonin (5-hydroxytryptamine or 5-HT).[31] Clinical trials, however, are regarded inconclusive and lacking.[32] Serotonin has a relatively short half-life since it is rapidly metabolized by monoamine oxidase.[citation needed]

Due to the conversion of 5-HTP into serotonin by the liver, there may be a significant risk of heart valve disease from serotonin's effect on the heart.[33][34]

It is marketed in Europe for depression and other indications under the brand names Cincofarm and Tript-OH. In the United States, 5-HTP does not require a prescription, as it is covered under the Dietary Supplement Act. Since the quality of dietary supplements is now regulated by the U.S. Food and Drug Administration, manufacturers are required to market products whose ingredients match the labeling, but are not required to establish efficacy of the product.[35]

The primary product of the liver enzyme tryptophan dioxygenase is kynurenine.[10][36]

In 1912 Felix Ehrlich demonstrated that yeast attacks the natural amino acids essentially by splitting off carbon dioxide and re-placing the amino group with hydroxyl. By this reaction, tryptophan gives rise to tryptophol.[37]

Tryptophan supplements and EMS

There was a large tryptophan-related outbreak of eosinophilia-myalgia syndrome (EMS) in 1989, which caused 1,500 cases of permanent disability and at least thirty-seven deaths. Some epidemiological studies[38][39][40] traced the outbreak to L-tryptophan supplied by a Japanese manufacturer, Showa Denko KK.[41] It was further hypothesized that one or more trace impurities produced during the manufacture of tryptophan may have been responsible for the EMS outbreak.[42][43] The fact that the Showa Denko facility used genetically engineered bacteria to produce L-tryptophan gave rise to speculation that genetic engineering was responsible for such impurities.[44] However, the methodology used in the initial epidemiological studies has been criticized.[45][46] An alternative explanation for the 1989 EMS outbreak is that large doses of tryptophan produce metabolites that inhibit the normal degradation of histamine, and excess histamine in turn has been proposed to cause EMS.[47]

Most tryptophan was banned from sale in the US in 1991, and other countries followed suit. Tryptophan from one manufacturer, of six, continued to be sold for manufacture of baby formulas. At the time of the ban, the FDA indicated to not have known that EMS was caused by a contaminated batch,[48] although they appear to have had knowledge of it, [49] and yet, even when the contamination was discovered and the purification process fixed, the FDA maintained that L-tryptophan is unsafe. In February 2001, the FDA loosened the restrictions on marketing (though not on importation), but still expressed the following concern:

"Based on the scientific evidence that is available at the present time, we cannot determine with certainty that the occurrence of EMS in susceptible persons consuming L-tryptophan supplements derives from the content of L-tryptophan, an impurity contained in the L-tryptophan, or a combination of the two in association with other, as yet unknown, external factors."[41]

Since 2002, L-tryptophan has been sold in the U.S. in its original form. Several high-quality sources of L-tryptophan do exist, and are sold in many of the largest healthfood stores nationwide. Indeed, tryptophan has continued to be used in clinical and experimental studies employing human patients and subjects.

In recent years in the U.S., compounding pharmacies and some mail-order supplement retailers have begun selling tryptophan to the general public. Tryptophan has also remained on the market as a prescription drug (Tryptan), which some psychiatrists continue to prescribe, in particular as an augmenting agent for people unresponsive to antidepressant drugs.[citation needed]

Turkey meat and drowsiness

A common assertion is that heavy consumption of turkey meat results in drowsiness, due to high levels of tryptophan contained in turkey.[50][51] However, the amount of tryptophan in turkey is comparable to that contained in most other meats.[17][51] Furthermore, post-meal drowsiness may have more to do with what else is consumed along with the turkey and, in particular, carbohydrates.[52] It has been demonstrated in both animal models[53] and humans[54][55][56] that ingestion of a meal rich in carbohydrates triggers release of insulin. Insulin in turn stimulates the uptake of large neutral branched-chain amino acids (BCAA), but not tryptophan (an aromatic amino acid) into muscle, increasing the ratio of tryptophan to BCAA in the blood stream. The resulting increased ratio of tryptophan to BCAA in the blood reduces competition at the large neutral amino acid transporter (which transports both BCAA and aromatic amino acids), resulting in the uptake of tryptophan across the blood–brain barrier into the cerebrospinal fluid (CSF).[57][58] Once in the CSF, tryptophan is converted into serotonin in the raphe nuclei by the normal enzymatic pathway.[53][55] The resultant serotonin is further metabolised into melatonin by the pineal gland.[9] Hence, this data suggests that "feast-induced drowsiness"— or postprandial somnolence — may be the result of a heavy meal rich in carbohydrates, which, via an indirect mechanism, increases the production of sleep-promoting melatonin in the brain.[53][54][55][56]


See also


  1. ;
  2. [dead link]
  3. 9.0 9.1 [dead link]
  4. 10.0 10.1
  5. Tryptophan background
  6. 17.0 17.1 17.2
  7. - The National Institute for Public Health and the Environment (Netherlands)
  8. 24.0 24.1
  9. 41.0 41.1
  10. FDA Tryptophan Recall
  11. 51.0 51.1
  12. 53.0 53.1 53.2
  13. 54.0 54.1
  14. 55.0 55.1 55.2
  15. 56.0 56.1

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