Plants and microorganisms commonly synthesize tryptophan from shikimic acid or anthranilate. 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.
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.
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 and depression. The authors did not find reduced tryptophan in lactose maldigestion. 
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.
There is evidence that blood tryptophan levels are unlikely to be altered by changing the diet, 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. Tryptophan has shown some effectiveness for treatment of a variety of other conditions typically associated with low serotonin levels in the brain. In particular, tryptophan has shown some promise as an antidepressant alone and as an "augmenter" of antidepressant drugs. However, the reliability of these clinical trials has been questioned because of lack of formal controls and repeatability. 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.
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.
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.
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.
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 traced the outbreak to L-tryptophan supplied by a Japanese manufacturer, Showa Denko KK. It was further hypothesized that one or more trace impurities produced during the manufacture of tryptophan may have been responsible for the EMS outbreak. 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. However, the methodology used in the initial epidemiological studies has been criticized. 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.
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, although they appear to have had knowledge of it,  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."
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.
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