One of the essential amino acids. It is a heterocyclic compound that is found in small amounts in most proteins. It plays an important role in the growth and development of infants and in the biosynthesis of serotonin and niacin (thus, deficiency of niacin or tryptophan can cause pellagra). Its occurrence in milk has been suggested as the reason that drinking milk before bedtime helps people sleep. It is used in medicine and nutrition research, in enriched foods, and as a dietary supplement.
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Tryptophan (abbreviated as Trp or W) is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in genetic code as the codon UGG. Only the L-stereoisomer of tryptophan is used in structural or enzyme proteins, but the D-stereoisomer is occasionally found in naturally produced peptides (for example, the marine venom peptide contryphan). The distinguishing structural characteristic of tryptophan is that it contains an indole functional group.
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 E. coli. The conversion is catalyzed by the enzyme tryptophan synthase.
For many organisms (including humans), 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, 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 and depression.
In bacteria that synthesize tryptophan, high cellular levels of this amino acid activate a repressor protein, which binds to the trp operon. 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.
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Clinical research has shown mixed results with respect to tryptophan's effectiveness as a sleep aid, especially in normal patients and for a growing variety of other conditions typically associated with low serotonin levels or activity in the brain such as premenstrual dysphoric disorder and seasonal affective disorder. In particular, tryptophan has been showing considerable promise as an antidepressant alone, and as an "augmenter" of antidepressant drugs. However, the reliability of these clinical trials has been questioned.
5-HTP readily crosses the blood-brain barrier and in addition is rapidly decarboxylated to serotonin (5-hydroxytryptamine or 5-HT) and therefore may be useful for the treatment of depression. However serotonin has a relatively short half-life since it is rapidly metabolized by monoamine oxidase, and therefore is likely to have limited efficacy. 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. However, since the quality of dietary supplements is 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.
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."
At the time of the ban, the FDA did not know, or did not indicate, that EMS was caused by a contaminated batch, 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:
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 health food 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, particularly as an augmenting agent for people who are unresponsive to antidepressant drugs.
It has been demonstrated in both animal models and in humans 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 (LNAA) but not tryptophan (trp) into muscle, increasing the ratio of trp to LNAA in the blood stream. The resulting increased ratio of tryptophan to large neutral amino acids in the blood 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 (CNS). Once inside the CNS, tryptophan is converted into serotonin in the raphe nuclei by the normal enzymatic pathway. The resultant serotonin is further metabolised into melatonin by the pineal gland. Hence, these data suggest that "feast-induced drowsiness," and in particular, the common post-Christmas and American post-Thanksgiving dinner drowsiness, 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.