Tryptophan

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Tryptophan
Systematic name	(S)-2-Amino-3-(1H-indol-3-yl)- propionic acid
Abbreviations	Trp W
Chemical formula	C11H12N2O2
Molecular mass	204.23 g mol−1
Melting point	289 °C
Density	1.34 g cm-3 (solid)
Isoelectric point	5.89
pKa	2.38 9.34
CAS number	[73-22-3]
EINECS number	200-795-6
SMILES	C(N)(C(=O)O)CC1c2ccccc2NC=1
Disclaimer and references

Tryptophan is an amino acid and essential in human nutrition. It is one of the 20 amino acids in the genetic code (codon UGG). Only the L-stereoisomer appears in mammalian protein, however the D-stereoisomer is occasionally found in natural materials (for example, the marine venom peptide contryphan^[1]).

[edit] Function

For many organisms tryptophan is an essential amino acid. This means that it cannot be synthesized by the organism and therefore must be part of its diet. Amino acids function as building blocks in protein biosynthesis.

Tryptophan is a precursor for serotonin (a neurotransmitter), melatonin (a neurohormone), and niacin. The functional group of tryptophan is indole; see that article for more on its chemical properties.

5-HTP, a metabolite of tryptophan, has been indicated as an aid for epilepsy and depression.^{[citation needed]}

[edit] Dietary sources

Tryptophan, found as a component of dietary protein, is particularly plentiful^[2] in oats, bananas, dried dates, milk, yogurt, cottage cheese, red meat, fish, poultry, sesame, chickpeas, sunflower seeds, pumpkin seeds, and peanuts. It is found in turkey at a level typical of poultry in general.

[edit] Use as a dietary supplement

For some time, tryptophan was available in health food stores as a dietary supplement. Since 2002, L-Tryptophan has been sold again in its original form. Many people found tryptophan to be a safe and reasonably effective sleep aid, probably due to its ability to increase brain levels of serotonin (a calming neurotransmitter when present in moderate levels) and/or melatonin (a sleep-inducing hormone secreted by the pineal gland in response to darkness or low light levels).^[3] Clinical research tended to confirm tryptophan's effectiveness as a natural sleep aid and for a growing variety of other conditions typically associated with low serotonin levels or activity in the brain.^{[citation needed]} (Particularly work by Dr. Richard Wurtman at MIT). In particular, tryptophan showed considerable promise as an antidepressant alone, and as an "augmenter" of antidepressant drugs. Other promising indications included relief of chronic pain and reduction of impulsive, violent, manic, addictive, obsessive, or compulsive behaviours and disorders.

A more recent study^[4] has shown that nighttime use "modestly but significantly reduced sleepiness (P = 0.013) and improved brain-sustained attention processes (P = 0.002) the following morning".

In 1989, a large outbreak of a new, disabling, and in some cases deadly autoimmune illness called eosinophilia-myalgia syndrome (EMS) was traced to L-tryptophan. The bacterial culture used to synthesize tryptophan by a major Japanese manufacturer, Showa Denko KK, had recently been synthesized to increase tryptophan production; with the higher tryptophan concentration in the culture medium, the purification process had also been streamlined to reduce costs, and a purification step that used charcoal absorption to remove impurities had been omitted. This allowed another bacterial metabolite through the purification, resulting in the presence of an end-product contaminant responsible for the toxic effects. The FDA was unable to establish with certainty that this was the sole cause of the outbreak. Tryptophan was banned from sale in the US, and other countries followed suit.

Though it is indisputable that Showa Denko KK did produce and sell a contaminated batch of L-tryptophan, there are some concerns^[5] that the FDA's handling of this accident unfairly favored the pharmaceutical industry and the new antidepressant Prozac if only because of its curiously fortuitous timing. The March 22, 1990 ban on public sale of L-tryptophan came only four days before the media announcement of Prozac on March 26, 1990 in Newsweek magazine^[6]. Both L-tryptophan and Prozac affect serotonin in the brain, though in different ways, and were promising in the treatment of depression. At the time of the ban the FDA did not know, or did not indicate, that EMS was caused by a contaminated batch^[7], and yet even when the contamination was discovered and the process fixed, the FDA maintained that L-tryptophan was 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."^[8]

In recent years, 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, particularly as an augmenting agent for people who are unresponsive to antidepressant drugs.^{[citation needed]} Also, most health-food stores sell a metabolite of tryptophan called 5-HTP to get around the resulting artificially high cost of the amino acid itself. But several high quality sources of L-Tryptophan do exist, and are sold in many of the largest health food stores nationwide. Indeed, tryptophan has continued to be used in clinical and experimental studies employing human patients and subjects. Several of these studies suggest tryptophan can effectively treat the fall/winter depression variant of seasonal affective disorder (SAD).^{[citation needed]}

[edit] Tryptophan and turkey

According to popular belief, eating tryptophan in turkey meat causes drowsiness. Turkey does contain tryptophan, which does have a documented sleep-inducing effect as it is readily converted into serotonin by the body. However, tryptophan is effective only when taken on its own as a dietary supplement. Tryptophan in turkey is found as part of a protein, and, in small enough amounts, this mechanism seems unlikely.^[9]

A more-likely hypothesis is that the ingestion of large quantities of food, such as at a Thanksgiving feast, means that large quantities of both carbohydrates and branched-chain amino acids are consumed. Like carbohydrates, branched-chain amino acids require insulin to be transduced through the myocyte membranes, which, after a large meal, creates a competition among the amino acids and glucose for insulin, while simultaneously creating tryptophan's reduced competition with other amino acids for the Large Neutral Amino Acid Transporter protein for transduction across the blood-brain barrier. The result is a greater availability of tryptophan, via the Large Neutral Amino Acid Transporter, for conversion into serotonin by the raphe nuclei, which is then available for conversion into melatonin by the pineal gland. Drowsiness is the result.

Alcoholic beverage consumption at holiday feasts is likely to compound the effect.

On average, a full grown male must consume some 45 pounds of turkey to have any narcoleptic effect.

[edit] Physiology

5-HTP, a metabolite of tryptophan, readily crosses the blood barrier, aiding in the treatment of depression.^{[citation needed]} It is marketed in Europe for this purpose under brand names like Cincofarm and Tript-OH.

Supplements do not require a prescription in America thanks to the Dietary Supplement Act. However, since the quality of dietary supplements are not regulated by the FDA, the quality of dietary and nutritional supplements tends to vary and there is no guarantee that the label accurately depicts what the bottle contains.^{[citation needed]}

[edit] Fictional references

• In James Cameron's TV series Dark Angel, genetically engineered Max Guevara and the other escaped X-5s need to take tryptophan supplements to control their seizures which were the result of a faulty gene.
• In an episode of Seinfeld, Jerry and George use turkey and boxed wine to cause Jerry's girlfriend to fall asleep so they can play with her extensive antique toy collection. When Jerry's girlfriend asks what is it in turkey that makes people drowsy, Jerry and George immediately and simultaneously respond "Tryptophan!"
• In the TV series Reno 911!, the faux-information documentary "Keeping it Real, Real Safe" claims that tryptophan is as dangerous as alcohol when it comes to driving.
• In the episode "Psycho Therapy" of the MTV animated series Daria, Daria tells her father, Jake, of tryptophan in milk and its calming influences. This serves as a running gag through the episode.

[edit] References

1. ^ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10471307&dopt=Abstract
2. ^ http://www.vitamins-supplements.org/amino-acids/tryptophan.php
3. ^ http://web.mit.edu/dick/www/pdf/92.pdf
4. ^ http://www.medscape.com/viewarticle/505203
5. ^ http://www.psrast.org/jftrypt.htm
6. ^ http://www.youngagain.com/enemies.html
7. ^ http://www.fda.gov/bbs/topics/NEWS/NEW00064.html
8. ^ http://vm.cfsan.fda.gov/~dms/ds-tryp1.html
9. ^ http://www.snopes.com/food/ingredient/turkey.asp

[edit] See also

• 5-hydroxytryptophan
• Tryptamines

[edit] External links

• Tryptophan catabolism (early stages)
• Tryptophan catabolism (later stages)
• Computational Chemistry Wiki
• Thanksgiving, Turkey, and Tryptophan
• FDA Information Paper on L-tryptophan and 5-hydroxy-L-tryptophan
• Snopes article debunking the turkey–drowsiness connection
• The FDA Ban of L-Tryptophan: Politics, Profits and Prozac
• Effects of Tryptophan Depletion on the Performance of an Iterated Prisoner's Dilemma Game in Healthy Adults - Nature Neuropsychopharmacology
• Tryptophan Repressor (Animation)
• Links to external chemical sources.