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**Title : Tryptophan and its Effects**
**Abstract** Tryptophan an essential amino acid plays many roles in body and helps to avoid certain problems like depression, anxiety, restless leg disorder, diet, etc. Once Tryptophan gets introduced in the body it gets converted into 5-HTP and Serotonin and then to niacin and melatonin. Serotonin helps improvising appetite, sleep, depression, mood and pain levels. So getting proper diet helps improvising Serotonin, a neurotransmitter in body and thus helping against all problems. History shows that Tryptophan came to point of banning by FDA in US and other countries due to people filing case for Eosinophilia-myalgia-syndrome(EMS). But the FDA’s research and investigation proved that it is essential amino acid for body which is not natural but it has to be taken with diet, and after getting right results, FDA took it out from “not generally recognized”, and allowed it into market it for general public. So Tryptophan has came into picture and is used to fight against several disorders and anxieties in body. **Introduction** Human body can produce 10 of the 20 amino acids. Other requirement must be supplied in the food. These are the essential amino acids absence of it causes performance of body means flow cycle of normal daily routine. It is not like stress and fat that human body is storing amino acids for later use so it has to be supplied to body for daily use through food. They are structural units that make up proteins. They create two types of chains depending upon length of chain, short polymer chains called peptides and longer chains called proteins. These polymers are linear and unbranched, with each amino acid within the chain attached to two neighboring amino acids. The process of making proteins is called translation (1). Below is the general structure of amino acids.

Figure 1. Structure of Amino Acids

Tryptophan is one of the 20 amino acids that very useful in human body for different purposes. Tryptophan was first discovered in 1901 by Sir Frederick Hopkins during hydrolysis of casein (1). Casein is phosphoprotein protein usually found in cow milk and cheese. This casein helps to produce Tryptophan. In nature, plants and microorganisms produced tryptophan on their own, while in human it comes through food. Tryptophan can also be synthesized by biochemical reaction of serine and indole using E-coli (2, 3). Tryptophan is amino acids used to synthesis the basic building blocks of protein but unlike some amino acids, tryptophan is considered one of the most essential. In biochemistry, the term amino acid are those amino group in which amino and carboxylate groups are attached to the same carbon, it is called α–carbon. The amino acids mostly occur in two possible isomers called D and L. The L amino acids represent all of the amino acids found in proteins, while D amino acids are found in nature. L amino acids are also called proteinogenic amino acids. Tryptophan contains a large rigid aromatic group on the side chain. Tryptophan's three letter code is Trp, its one letter code is W, its codon is UGG, and its systematic name is 2-Amino-3-(lH-indol-3-yl)-propanoic acid (IUPAC-IUB 1983) (4). Figure 2: Structure of Tryptophan

Tryptophan plays important role for the development and functioning of many organs in the body. It is an essential precursor to the neurotransmitter such as for serotonin and melatonin in the brain. The serotonin is released from brain neurons, which depends upon 5-HT synthesis, and indirectly on precursor tryptophan. Tryptophan is the key ingredient in making serotonin because it is the only substance that can be converted into Serotonin. Serotonin is synthesized via tryptophan hydroxylase. Tryptophan is converted to Serotonin in a two-step process. First, Tryptophan is converted into 5-hydroxy L-Tryptophan (5-HTP) and then 5-HTP is then converted into Serotonin (5). Serotonin is a neurotransmitter, involved in the impulses. Release of serotonin causes the nerve to carry messages from one nerve cell to other cells. Serotonin is then converted into melatonin. It is also a two step process. First Serotonin is converted to N-acetyl 5-HT and then N-acetyl 5-HT converted to melatonin. These are derived from the known dependence of 5-HT synthesis on the local concentration of tryptophan and in addition it derives from studies reporting modifications in certain behaviors, including aggression and pain sensitivity, this study was conducted in living organisms (vivo) and non living organisms (vitro). The altering levels of tryptophan in living organisms results in the sensitivity of tryptophan and other behaviors like aggressiveness, tingling, numbness, etc (2,3). Foods with the richest dietary in tryptophan are chocolate, oats, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, polutry, sesame, chickpeas, sunflower seeds, pumkin seeds, spirulina and peanuts (1). As shown below is synthesis process that how tryptophan is created fig A is synthesis and fig B is bio synthesis process through which Tryptophan is generated.
 * Effects of Tryptophan**

Tryptophan is important amino acid for keeping biochemical balance in the brain, and is very helpful for sleep deprivation, anxiety and mood enhancement which observed due to low serotonin levels. There are no side effects for Tryptophan as it taken directly, however some people may experience mild nausea, constipation, gas, drowsiness, or a decrease in sex drive. On the contrary this amino acid is helpful in appetite control, pain tolerance and with jet lag. The following are the positive/negative effects of Tryptophan. //Seasonal affective disorder:// In treatment of Seasonal affective disorder, light therapy is replaced by Tryptophan. Studies shows that effectiveness of Light therapy is not giving that much relief compare to relief given by tryptophan. Level of serotonin plays important role in the path physiology of seasonal affective disorder/winter type (SAD). The present study shows that dose of tryptophan helps to improve condition of patients that suffer from SAD, recover very well from depression. This proved an importance of serotonin in the pathophysiology of SAD (6, 7). //Emotional behavior:// Serotonin is playing important role in determining emotional information in conscious and unconscious activity. Acute tryptophan depletion (ATD) used to determine this role(8). Study held on female volunteer that shows ATD attenuates the information about positive faces and the negative intensity of threatening faces. Face processing is an important to women social life, as it carries lots of socially relevant information above identity, gender and age, by also signaling emotional state, intentions and sexual fitness. //Depression and regulation of appetite:// Tryptophan is also helpful in synthesis of protein, studies shows that the food taken at dinner time having 70% carbohydrates which increase a level of tryptophan and thus help in diet and also helps to calm down neurotransmitter of brain and let a human sleep at night peacefully. So that means low level of tryptophan may cause depression and diet problems in human being. High amount of tryptophan helps you regulate your appetite; mood and helping you getting better sleep. Tryptophan found in all foods that contain protein, the amount is small compared to other essential amino acids. Red meat, dairy products, nuts, seeds, bananas, soybeans and soy products, tuna, shellfish, and turkey are the few examples of where tryptophan can be easily found. It is proved that brain serotonin systems are responsible for modulating neural circuits that regulate emotion and mood in humans, which is the reason that it is playing a key role in the pathophysiology and treatment of depression. The way to study brain serotonin function is the tryptophan depletion (TD) (9, 10). The synthesis of serotonin in the brain is dependent on the availability of its amino acid precursor tryptophan from plasma. It is possible to lower a level of tryptophan availability to the brain by giving food that have a low amount of tryptophan. This results in low concentration of tryptophan in plasma and inhibits transport across the blood-brain barrier. And resulting in, brain serotonin synthesis and release decrease. If impaired serotonin function plays an important part in the pathophysiology of major depressive disorder, so it is expected that a continuously decreasing level of tryptophan in the plasma of people who are vulnerable to major depression might results in increasing level of depressive symptoms. Causes of depression are imbalance of setononin (tryptophan). The antidepressant is increases the balance by blocking their breakdown. Normally Dose of 1 to 3gm per day issued to treat a variety of depression syndromes. Very effective when depression is accompanied by insomnia. Tryptophan effects very well on Depression associated with menstrual cycles and postpartum depression. //Drowsiness:// Lower dose of Serotonin causes side effects like drowsiness and headaches in those people whose daily dose level increase up to required level (1). The best example of it is heavy consumption of turkey meat (Thankgiving or Christmas feast) which results in drowsiness. The only reason being that it contains high levels of tryptophan. The level is not that much high compare to other meats. These results in different amino acid called large neutral branched-chain amino acids (LNAA) but not tryptophan (trp).The increased ratio of tryptophan to large neutral amino acids in the blood reduces flow of tryptophan across the blood-brain barrier into the central nervous system (CNS). So as a result serotonin is further metabolized into melatonin and results in drowsiness. //Anxiety disorder:// In many research studies have shown that the person with anxiety disorder have a low level of serotonin (tryptophan). So anxiety is under serotonergic control. This is the reason behind using tryptophan depletion on CO-2 induced panic in anxiety-related mechanisms and on patients with anxiety disorders (11, 12). //Panic Disorder:// Tryptophan is very useful in evaluating function of serotonin in psychiatric disease. Panic Disorder treatment and its study show that neurotransmission function of serotonin or 5-HTP is responsible for it. Level of 5-HTP which is converted through tryptophan helps to maintain panic genes through intermediate chemical processes (11, 12). Tryptophan also plays important role in the following: //Asthma:// The dose of Tryptophan is not recommended for people who are having Asthma (13), because while taking a food that has a high tryptophan, causes creation of asthmatics the main agent behind Asthma. So tryptophan is removed from a food before it is given to patient. //Tourette Sydrome//:

Tourette is Sydrome which is quite similar to obsessive/compulsive in many ways may have good response to tryptophan; but it is yet to determined. This kind of effect observed during early childhood, it decreases frequency and severity in adolescence and early adulthood. Usually drugs are given to overcome these problems. (13)

//Restless leg syndrome:// Restless leg syndrome, metabolic sleep disorder which causes numbness, tingling, tiredness and itching in legs, Study shows that tryptophan is helpful to RLS sufferers (13). This normally happens during sleep or rest position and it observed in lower part of legs. It is not affecting anybody’s health but long time presence of it creates drowsiness in body.

**Tryptophan supplements and its Future** Starting from its invention in 1901, the study and research was continued till 1974, because of health related issues U.S Food and Drug Administration (FDA), and Food department of Canada declared it as not generally recognized as safe, but they were not stop prohibiting it until issues came with Eosinophilia-myalgia-syndrome in 1989. Eosinophilia-myalgia-syndrome (EMS) was came into picture and it was firmly belief that the manufacturer from Japan, Showa Denko was the reason. Investigation shows 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. So due to following suit it was banned from sale in 1991, in US and other countries. Investigation was still in process and there was no firm reason behind that ban, because of that FDA kept ban till 2001. Studies show that there are no significant amounts of free amino acids in human body, it has to be taken in certain way to avoid efficacy in body this was the reason that FDA has to taken out it from “Not Generally recognized”, after that the ban was released on marketing but with certain concern defined by FDA. **Conclusion** As stated Tryptophan is an essential amino acid and as such, body is not able to manufacture it and must get it from various food sources or through drug that contains certain percentage of tryptophan which helps to improvise condition. Once ingested in to body, tryptophan increases brain levels of serotonin, a neurotransmitter which impact in different ways in body. Tryptophan is responsible for increasing the levels of melatonin, a hormone secreted by the pineal gland, which ultimately induces sleep. It is helpful to body in improvising conditions. 1. [|Source] 2. Judith D. Schaechter and Richard J. Wurtman. Serotonin release varies with brain tryptophan levels. //Brain Research// 1990; 532: 203-210. doi:10.1016/0006-8993(90)91761-5 3. Jill K. Stoneman, FNP and James W. Banks, MD. Serotonin and Headache: Using L-Tryptophan, 5-HTP and Other Methods to Increase Brain Serotonin Levels. //American Headache Society// 2006.[|Source] 4. [] 5. Elaine R. Radwanski and Robert L. Last. Tryptophan Biosynthesis and Molecular Genetics. //American Society of Plant Physiologists//,1995; 7: 921-934 [|Source] 6. Nicole Praschak-Rieder, Alan A. Wilson, Douglas Hussey, Anna Carella, Corie Wei, Nathalie Ginovart, Markus J. Schwarz, Johanna Zach, Sylvain Houle, and Jeffrey H. Meyer. Effects of Tryptophan Depletion on the Serotonin Transporter in Healthy Humans. //Biological Psychiatry// 2005; 58: 825–830 doi:10.1016/j.biopsych.2005.04.038 7. Felix D. C. C. Beacher & Marcus A. Gray & Ludovico Minati & Richard Whale & Neil A. Harrison & Hugo D. Critchley. Acute tryptophan depletion attenuates conscious appraisal of social emotional signals in healthy female volunteers. // Psychopharmacology. // 2010. DOI 10.1007/s00213-010-1897-5 [|Source] 8. K A Smith, C G Fairburn, P J Cowen. Relapse of depression after rapid depletion of tryptophan //The Lancet// 1997; 349: 915–919. doi:10.1016/S0140-6736(96)07044-4 9. B.Y. Silber, J.A.J. Schmitt. Effects of tryptophan loading on human cognition, mood, and sleep. //Neuroscience and Biobehavioral// Reviews 2010; 34: 387 – 407. doi:10.1016/j.neubiorev.2009.08.005 10. M. J. Attenburrow C. Williams, J. Odontiadis, J. Powell, F. Van De Ouderraa, M. Williams and P. J. Cowen. The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function. //Psychological Medicine,// 2003; 33, 1381–1386. DOI: 10.1017/S0033291703008547. [|Source] 11.Tineke klaaseen, Jurjen Klumperbreek, Nicolaas, E.P. Deutz, Herman M. van Praad and Eric Griez **. ** Effects of tryptophan depletion on anxiety and on panic provoked by carbon dioxide challenge. //Psychiatry research// 1998; 77 :167-174. [|Source] 12.Andrew W. Goddard, Diane E. Sholomskas, Katherine E. Walton, Francine M. Augeri, Dennis S. Charney, George R. Heninger, Wayne K. Goodman and Lawrence H. Price**. ** Effects of tryptophan depletion in panic disorder. //Biological Psychiatry. 1//994; 36(11):775-777.[|Source] 13. Source 14. Victor Herbert. L-Tryptophan-A medicolegal case against over-the-counter marketing the supplements of amino acids. //Nutrition today// 1992.[|Source]
 * References**