Tryptophan

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Tryptophan is an amino acid and essential in human nutrition. It is one of the 20 amino acids encoded by the genetic code (as 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]).

Contents 1 Function 2 Dietary sources 2.1 Use as a dietary supplement 2.2 Tryptophan and turkey 2.3 Physiology 3 Fluorescence 4 Fictional references 5 References 6 See also 7 External links

[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 suggested as an aid for epilepsy^[2] and depression though clinical trials are inconclusive and lacking.^[3]

[edit] Dietary sources

Tryptophan, found as a component of dietary protein, is particularly plentiful^[4] in chocolate, oats, bananas, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas, sunflower seeds, pumpkin seeds,spirulina and peanuts. It is found in turkey at a level typical of poultry in general^{[citation needed]}.

[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).^[5] 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. (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, anxiety-related, obsessive, and compulsive behaviours and disorders. Recent studies suggests that it can even help relieve tinnitus, due to the serotonin production.^[6]

A more recent study^[7] 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 one source of L-tryptophan. The bacterial culture used to synthesize tryptophan by a major Japanese manufacturer, Showa Denko KK, had been genetically modified several times to increase tryptophan production during the 1980s.^[8] Along with the higher tryptophan concentrations in the modified culture media, the purification process had also been streamlined to reduce costs, and a purification step that used charcoal absorption to remove some impurities had been omitted. The manufacturer maintained that this process modification allowed another bacterial metabolite through the purification, resulting in the presence of an end-product contaminant responsible for the toxic effects. As of 1996, Showa Denko had destroyed all modified organisms without FDA receipt of culture samples.^[9][10] The FDA was unable to publicly establish with certainty what contaminant was the cause of the outbreak.

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. A Rutgers Law Journal article observed, “Political pressures have played a role in the FDA’s decision to ban L-tryptophan as well as its desire to increase its regulatory power over dietary supplements.”^[11]

Though it is indisputable that Showa Denko KK did produce and sell a contaminated batch of L-tryptophan, there are some concerns^[12] that the FDA's handling of this accident unfairly favored the pharmaceutical industry, genetically modified organisms' safety record^[13] 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^[14]. 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^[15], and yet even when the contamination was discovered and the purification 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."^[16]

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, ingestion of turkey alone has not been proven to have this effect. An additional hypothetical mechanism is as follows: A large quantity of any food,^{[original research?]} such as a Thanksgiving feast, introduces large quantities of both carbohydrates and branched-chain amino acids releasing insulin. Insulin stimulates the uptake of large neutral branched-chain amino acids (and not tryptophan) by muscle cells through the myocyte membranes. The result is an increase in the ratio of tryptophan to large neutral amino acids in the blood. This reduces competition with other amino acids for the Large Neutral Amino Acid Transporter protein for uptake of tryptophan across the blood-brain barrier into the central nervous system. Once inside the central nervous system, tryptophan is converted into serotonin by the raphe nuclei, and serotonin is further metabolised into melatonin by the pineal gland.

Alcoholic beverage consumption at holiday feasts is likely to compound the effect.^{[original research?]}

On average, a full grown male must consume some 45 pounds of turkey to have any narcoleptic effect.^{[citation needed]}

L-tryptophan is mentioned in natural causes by Dan Hurly.^{[citation needed]}

[edit] Physiology

5-HTP, a metabolite of tryptophan, readily crosses the blood brain 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.

In the United States, 5-HTP does not require a prescription as it is covered under 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] Fluorescence

The fluorescence of a folded protein is a mixture of the fluorescence from individual aromatic residues. Most of the intrinsic fluorescence emissions of a folded protein are due to excitation of tryptophan residues, with some emissions due to tyrosine and phenylalanine. Typically, tryptophan has a wavelength of maximum absorption of 280 nm and a wavelength of maximum fluorescence emission of 350 nm, although these values can be dependent on various factors such as the solvent used. Also, when tryptophans are located within proteins, factors such as whether the tryptophan is buried and proximity of other residues (i.e. nearby protonated acidic groups such as Asp or Glu can cause quenching of Trp fluorescence) can also influence fluorescence characteristics. ^[17]

[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.
• In the TV series "Titus", Christopher Titus believed it was tryptophan that caused sleepiness during a turkey dinner. It was in fact the bottle of antidepressants his mother put in their food.

[edit] References

1. ^ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10471307&dopt=Abstract
2. ^ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=148040
3. ^ http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16023217
4. ^ http://www.vitamins-supplements.org/amino-acids/tryptophan.php
5. ^ http://web.mit.edu/dick/www/pdf/92.pdf
6. ^ Scientific American Mind, February issue
7. ^ http://www.medscape.com/viewarticle/505203
8. ^ Jeffrey M. Smith (September 2003) Seeds of Deception: Exposing Industry and Government Lies About the Safety of the Genetically Engineered Foods You're Eating. Yes! Books. ISBN-10: 0972966579
9. ^ James Maryanski. FDA. July 5, 1996.
10. ^ Page S. Center for Food Safely and Applied Nutrition, FDA, Congressional Hearing, Subcommittee, July 18, 1991.
11. ^ Beisler JH. Dietary Supplements and Their Discontents: FDA Regulation and the Dietary Supplement Health and Education Act of 1994(L-tryptophan section), Rutgers Law Journal, Winter 2000.
12. ^ http://www.psrast.org/jftrypt.htm
13. ^ Raphals P. Does medical mystery threaten biotech Science, vol. 249, no. 619, 1990.
14. ^ http://www.youngagain.com/enemies.html
15. ^ http://www.fda.gov/bbs/topics/NEWS/NEW00064.html
16. ^ http://vm.cfsan.fda.gov/~dms/ds-tryp1.html
17. ^ http://dwb.unl.edu/Teacher/NSF/C08/C08Links/pps99.cryst.bbk.ac.uk/projects/gmocz/fluor.htm

[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
• Links to external chemical sources

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