Tryptophan Totally Explained

Everything about Tryptophan totally explained

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.

Isolation

The isolation of tryptophan was first reported by Sir Frederick Hopkins in 1901 through hydrolysis of casein. From 600 grams of crude casein one obtains 4-8 grams of tryptophan.

Biosynthesis and industrial production

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 E. coli. The conversion is catalyzed by the enzyme tryptophan synthase.

Function

For many organisms (including humans), tryptophan is an essential amino acid. This means that it can't 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):

Serotonin (a neurotransmitter), synthesized via tryptophan hydroxylase. Serotonin, in turn, can be converted to melatonin (a neurohormone), via N-acetyltransferase and 5-hydroxyindole-O-methyltransferase activities.
Niacin is synthesized from tryptophan via kynurenine and quinolinic acids as key biosynthetic intermediates.

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.

Dietary sources

Tryptophan is a routine constituent of most protein-based foods or dietary proteins. It is particularly plentiful in chocolate, oats, bananas, mangoes, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas, sunflower seeds, pumpkin seeds, spirulina, and peanuts. It is also found in turkey at a level typical of poultry in general. >

Food	Protein [g/100g of food]	Tryptophan [g/100g of food]	Tryptophan/Protein [%]
turkey	21.89	0.24	1.11
cheese, cheddar	24.90	0.32	1.29
cheese, Parmesan	37.90	0.56	1.47
chicken	20.85	0.24	1.14
beef	20.13	0.23	1.12
lamb, chop	18.33	0.21	1.17
pork, chop	19.27	0.25	1.27
salmon	19.84	0.22	1.12
perch, Atlantic	18.62	0.21	1.12
caviar	24.60	0.32	1.30
sesame seed	17.00	0.37	2.17
sunflower seed	17.20	0.30	1.74
milk	3.22	0.08	2.34
egg	12.58	0.17	1.33
wheat flour, white	10.33	0.13	1.23
potatoes, russet	2.14	0.02	0.84
rice, white	7.13	0.08	1.16
banana	1.03	0.009	0.87

Use as a dietary supplement

For some time, tryptophan has been available in health food stores as a dietary supplement, although it's common in dietary protein. 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).
Clinical research tends to confirm tryptophan's effectiveness as a sleep aid 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.

Metabolites

5-Hydroxytryptophan (5-HTP), a metabolite of tryptophan, has been suggested as a treatment for epilepsy and depression, although clinical trials are regarded inconclusive and lacking.
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's 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 doesn't require a prescription, as it's covered under the Dietary Supplement Act. However, since the quality of dietary supplements isn't regulated by the FDA, the quality of dietary and nutritional supplements tends to vary, and there's no guarantee that the label accurately depicts what the bottle contains.

Tryptophan supplements and EMS

Although currently available for purchase, in 1989 a large outbreak (1500 cases of permanent disability including at least 37 deaths) of a disabling autoimmune illness called eosinophilia-myalgia syndrome (EMS) was traced by some epidemiological studies 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. However, many people who consumed Showa Denko L-tryptophan didn't develop EMS and cases of EMS have occurred prior to and after the 1989 epidemic. Furthermore 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 which 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. 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 didn't know, or didn't 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: � "Based on the scientific evidence that's available at the present time, we can't 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." While turkey does contain high levels of tryptophan, the amount is comparable to that contained in most other meats. 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. Hence, protein fluorescence may be used as a diagnostic of the conformational state of a protein. Furthermore, tryptophan fluorescence is strongly influenced by the proximity of other residues (for example, nearby protonated groups such as Asp or Glu can cause quenching of Trp fluorescence). Also, energy transfer between tryptophan and the other fluorescent amino acids is possible, which would affect the analysis, especially in cases where the Förster acidic approach is taken. In addition, tryptophan is a relatively rare amino acid; many proteins contain only one or a few tryptophan residues. Therefore, tryptophan fluorescence can be a very sensitive measurement of the conformational state of individual tryptophan residues. The advantage compared to extrinsic probes is that the protein itself isn't changed. The use of intrinsic fluorescence for the study of protein conformation is in practice limited to cases with few (or perhaps only one) tryptophan residues, since each experiences a different local environment, which gives rise to different emission spectra.

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