Tryptophan
Encyclopedia
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid
in the human
diet. It is encoded in the standard 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 peptide
s (for example, the marine venom peptide
contryphan
). The distinguishing structural characteristic of tryptophan is that it contains an indole
functional group. It is an essential amino acid as demonstrated by its growth effects on rats
.
in 1901 through hydrolysis
of casein
. From 600 gram
s of crude casein one obtains 4-8 grams of tryptophan.
s 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
.
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 disorders fructose malabsorption
and lactose intolerance
cause 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.
, oat
s, dried date
s, milk
, yogurt, cottage cheese
, red meat
, eggs
, fish
, poultry
, sesame
, chickpea
s, sunflower seeds, pumpkin seeds, corn
, spirulina, and peanut
s. Despite popular belief that turkey
has a particularly high amount of tryptophan, the amount of tryptophan in turkey is typical of most poultry.
Other herbs/plants containg tryptophan include Oenothera biennis
seeds, Helianthus annuus seed, Lablab purpureus,Nasturtium officinale and Psophocarpus tetragonolobus seed and leaf.
. 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 has shown mixed results with respect to tryptophan's effectiveness as a sleep aid
, especially in normal patients. Furthermore tryptophan has shown some effectiveness for treatment of a variety of other conditions typically associated with low serotonin levels in the brain such as premenstrual dysphoric disorder
and seasonal affective disorder
. In particular, tryptophan has shown 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), has been suggested as a treatment for epilepsy
and depression
, although clinical trials are regarded inconclusive and lacking. Since 5-HTP readily crosses the blood-brain barrier
and in addition is rapidly decarboxylated
to serotonin
(5-hydroxytryptamine or 5-HT), it may be useful for the treatment of depression. However, serotonin has a relatively short half-life since it is rapidly metabolized by monoamine oxidase
.
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. As 5-HTP is usually converted to serotonin
before it can reach the brain, elevating blood serotonin levels greatly, it may cause diarrhea and heart problems, while only slightly increasing brain serotonin. In Europe, 5-HTP is prescribed with Carbidopa
to delay the conversion of 5-HTP into serotonin until it reaches the brain (5-HTP is more effectively used when in conjunction with a dopa decarboxylase inhibitor such as Carbidopa
, which slows its conversion to serotonin, allowing more of the supplement to reach the brain).
It is marketed in Europe for depression and other indications under the brand names Cincofarm, Tript-OH and Optimax (UK). 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 there is now a guarantee that the label accurately depicts what the bottle contains.
(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 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 is 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 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 psychiatrist
s continue to prescribe, in particular as an augmenting agent for people unresponsive to antidepressant drugs.
or Christmas
feast) results in drowsiness
, which has been attributed to high levels of tryptophan contained in turkey. However, while turkey does contain high levels of tryptophan, the amount is comparable to that contained in most other meats.
Furthermore, post-meal drowsiness on Thanksgiving may have more to do with what else is consumed along with the turkey and, in particular, carbohydrate
s. It has been demonstrated in both animal models and 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
(BCAA), but not tryptophan (an aromatic amino acid) into muscle, increasing the ratio of tryptophan to BCAA in the blood stream. The resulting increased ratio of tryptophan to BCAA in the blood reduces competition at the large neutral amino acid transporter (which transports both BCAA and aromatic amino acids), resulting in the uptake of tryptophan across the blood-brain barrier
into the cerebrospinal fluid
(CSF). Once in the CSF, 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, this data suggest that "feast-induced drowsiness"—and, in particular, the common post-Christmas and North 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.
, which was suggested to retard the aging process. Rats on tryptophan-reduced diets have shown increased maximum life span
and improved biomarkers of aging (although the rate of initial deaths was higher than in controls). The result was attributed to harmful effects of the age-related increase in brain serotonin.
Essential amino acid
An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet.-Essentiality vs. conditional essentiality in humans:...
in the human
Human
Humans are the only living species in the Homo genus...
diet. It is encoded in the standard genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
as the codon UGG. Only the L-stereoisomer of tryptophan is used in structural
Fibrous protein
Scleroproteins, or fibrous proteins, constitute one of the three main classes of proteins, alongside globular proteins and conjugated proteins.Keratin, collagen, elastin, and fibroin are all scleroproteins...
or enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
proteins, but the D-stereoisomer is occasionally found in naturally produced peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s (for example, the marine venom peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
contryphan
Contryphan
The contryphans are a family of peptides that are active constituents of the poisonous venom produced by cone snail . The two amino acid cysteine residues in contryphans are linked by a disulfide bond...
). The distinguishing structural characteristic of tryptophan is that it contains an indole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...
functional group. It is an essential amino acid as demonstrated by its growth effects on rats
Animal testing on rodents
Rodents are commonly used in animal testing, particularly guinea pigs, hamsters, gerbils, rats, and mice.-The statistics:In the UK in 2004, 1,910,110 mice, 464,727 rats and 37,475 other rodents were used...
.
Isolation
The isolation of tryptophan was first reported by Frederick HopkinsFrederick Hopkins
Sir Frederick Gowland Hopkins OM FRS was an English biochemist who was awarded the Nobel Prize in Physiology or Medicine in 1929, with Christiaan Eijkman, for the discovery of vitamins. He also discovered the amino acid tryptophan, in 1901...
in 1901 through hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
of casein
Casein
Casein is the name for a family of related phosphoprotein proteins . These proteins are commonly found in mammalian milk, making up 80% of the proteins in cow milk and between 60% and 65% of the proteins in human milk....
. From 600 gram
Gram
The gram is a metric system unit of mass....
s of crude casein one obtains 4-8 grams of tryptophan.
Biosynthesis and industrial production
Plants and microorganismMicroorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
s commonly synthesize tryptophan from shikimic acid
Shikimic acid
Shikimic acid, more commonly known as its anionic form shikimate, is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi , from which it was first isolated....
or anthranilate
Anthranilic acid
Anthranilic acid is the organic compound with the formula C6H4COOH. This amino acid is a white solid when pure, although commercial samples may appear yellow. The molecule consists of a benzene ring with two adjacent functional groups, a carboxylic acid and an amine...
. The latter condenses with phosphoribosylpyrophosphate (PRPP), generating pyrophosphate
Pyrophosphate
In chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Any salt or ester containing two phosphate groups is called a diphosphate. As a food additive, diphosphates are known as E450.- Chemistry :...
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
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...
. In the last step, tryptophan synthase catalyzes the formation of tryptophan from indole and the amino acid serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
.
The industrial production of tryptophan is also biosynthetic and is based on the fermentation of serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
and indole
Indole
Indole is an aromatic heterocyclic organic compound. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring. Indole is a popular component of fragrances and the precursor to many pharmaceuticals. Compounds that contain an...
using either wild-type or genetically modified bacteria such as B. amyloliquefaciens
Bacillus amyloliquefaciens
Bacillus amyloliquefaciens is a species of bacteria that is the source of the BamH1 restriction enzyme. It also synthesizes a natural antibiotic protein barnase, a widely studied ribonuclease that forms a famously tight complex with its intracellular inhibitor barstar.-Discovery and name:B...
, B. subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...
, C. glutamicum or E. coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
. 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
Tryptophan synthase
Tryptophan synthase or tryptophan synthetase is an enzyme that catalyzes the final two steps in the biosynthesis of tryptophan. It is commonly found in Eubacteria, Archaebacteria, Protista, Fungi, and Plantae. However, it is absent from animalia. It is typically found as an α2β2 tetramer...
.
Function
Essential amino acid
An essential amino acid or indispensable amino acid is an amino acid that cannot be synthesized de novo by the organism , and therefore must be supplied in the diet.-Essentiality vs. conditional essentiality in humans:...
. 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
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
. In addition, tryptophan functions as a biochemical precursor
Precursor (chemistry)
In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....
for the following compounds (see also figure to the right):
- SerotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(a neurotransmitterNeurotransmitterNeurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
), synthesized via tryptophan hydroxylaseTryptophan hydroxylaseTryptophan hydroxylase is an enzyme involved in the synthesis of the neurotransmitter serotonin. TPH catalyzes the following chemical reactionIt employs one cofactor, iron.- Function :...
. Serotonin, in turn, can be converted to melatoninMelatoninMelatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
(a neurohormoneNeurohormoneA neurohormone is any hormone produced and released by neurons.Examples include:*Thyrotropin-releasing hormone *Gonadotropin-releasing hormone *Adrenocorticotropin-releasing hormone*Oxytocin*Antidiuretic hormone *Epinephrine...
), via N-acetyltransferaseN-AcetyltransferaseN-acetyltransferase is an enzyme that catalyzes the transfer of acetyl groups from acetyl-CoA to arylamines. They have wide specificity for aromatic amines, particularly serotonin, and can also catalyze acetyl transfer between arylamines without CoA. EC 2.3.1.5....
and 5-hydroxyindole-O-methyltransferase activities. - NiacinNiacin"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
is synthesized from tryptophan via kynurenineKynurenineL-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...
and quinolinic acidQuinolinic acidQuinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically, or with acidic hydrogen peroxide.Quinolinic acid is a downstream kynurenine pathway metabolite of tryptophan...
s as key biosynthetic intermediates. - AuxinAuxinAuxins are a class of plant hormones with some morphogen-like characteristics. Auxins have a cardinal role in coordination of many growth and behavioral processes in the plant's life cycle and are essential for plant body development. Auxins and their role in plant growth were first described by...
(a phytohormone) when sieve tube elements undergo apoptosisApoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
tryptophan is converted to auxins.
The disorders fructose malabsorption
Fructose malabsorption
Fructose malabsorption, formerly named "dietary fructose intolerance," is a digestive disorder in which absorption of fructose is impaired by deficient fructose carriers in the small intestine's enterocytes. This results in an increased concentration of fructose in the entire intestine.Fructose...
and lactose intolerance
Lactose intolerance
Lactose intolerance, also called lactase deficiency or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk...
cause 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
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
protein, which binds to the trp operon
Trp operon
Trp operon is an operon - a group of genes that are used, or transcribed, together - that codes for the components for production of tryptophan. The Trp operon is present in many bacteria, but was first characterized in Escherichia coli. It is regulated so that when tryptophan is present in the...
. 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 chocolateChocolate
Chocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...
, oat
Oat
The common oat is a species of cereal grain grown for its seed, which is known by the same name . While oats are suitable for human consumption as oatmeal and rolled oats, one of the most common uses is as livestock feed...
s, dried date
Date Palm
The date palm is a palm in the genus Phoenix, cultivated for its edible sweet fruit. Although its place of origin is unknown because of long cultivation, it probably originated from lands around the Persian Gulf. It is a medium-sized plant, 15–25 m tall, growing singly or forming a clump with...
s, milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...
, yogurt, cottage cheese
Cottage cheese
Cottage cheese is a cheese curd product with a mild flavor. It is drained, but not pressed, so some whey remains and the individual curds remain loose. The curd is usually washed to remove acidity, giving sweet curd cheese. It is not aged or colored. Different styles of cottage cheese are made from...
, red meat
Red meat
Red meat in traditional culinary terminology is meat which is red when raw and not white when cooked. In the nutritional sciences, red meat includes all mammal meat. Red meat includes the meat of most adult mammals and some fowl ....
, eggs
Egg (food)
Eggs are laid by females of many different species, including birds, reptiles, amphibians, and fish, and have probably been eaten by mankind for millennia. Bird and reptile eggs consist of a protective eggshell, albumen , and vitellus , contained within various thin membranes...
, fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
, poultry
Poultry
Poultry are domesticated birds kept by humans for the purpose of producing eggs, meat, and/or feathers. These most typically are members of the superorder Galloanserae , especially the order Galliformes and the family Anatidae , commonly known as "waterfowl"...
, sesame
Sesame
Sesame is a flowering plant in the genus Sesamum. Numerous wild relatives occur in Africa and a smaller number in India. It is widely naturalized in tropical regions around the world and is cultivated for its edible seeds, which grow in pods....
, chickpea
Chickpea
The chickpea is a legume of the family Fabaceae, subfamily Faboideae...
s, sunflower seeds, pumpkin seeds, corn
Corn
Corn is the name used in the United States, Canada, and Australia for the grain maize.In much of the English-speaking world, the term "corn" is a generic term for cereal crops, such as* Barley* Oats* Wheat* Rye- Places :...
, spirulina, and peanut
Peanut
The peanut, or groundnut , is a species in the legume or "bean" family , so it is not a nut. The peanut was probably first cultivated in the valleys of Peru. It is an annual herbaceous plant growing tall...
s. Despite popular belief that turkey
Turkey (bird)
A turkey is a large bird in the genus Meleagris. One species, Meleagris gallopavo, commonly known as the Wild Turkey, is native to the forests of North America. The domestic turkey is a descendant of this species...
has a particularly high amount of tryptophan, the amount of tryptophan in turkey is typical of most poultry.
| Food | Protein [g/100 g of food] |
Tryptophan [g/100 g of food] |
Tryptophan/Protein [%] |
|---|---|---|---|
| egg, white, dried | |
|
|
| spirulina, dried | |
|
|
| cod, atlantic, dried | |
|
|
| soybeans, raw | |
|
|
| pumpkin seed | |
|
|
| cheese, Parmesan | |
|
|
| caribou | |
|
|
| sesame seed | |
|
|
| cheese, cheddar | |
|
|
| sunflower seed | |
|
|
| pistacio | |
|
|
| cashew | |
|
|
| pork, chop | |
|
|
| turkey | |
|
|
| chicken | |
|
|
| beef | |
|
|
| salmon | |
|
|
| lamb, chop | |
|
|
| perch, Atlantic | |
|
|
| almond | |
|
|
| egg | |
|
|
| wheat flour, white | |
|
|
| baking chocolate, unsweetened | |
|
|
| milk | |
|
|
| rice, white | |
|
|
| oatmeal, cooked | |
|
|
| potatoes, russet | |
|
|
| banana | |
|
|
Other herbs/plants containg tryptophan include Oenothera biennis
Oenothera biennis
Oenothera biennis is a species of Oenothera native to eastern and central North America, from Newfoundland west to Alberta, southeast to Florida, and southwest to Texas, and widely naturalized elsewhere in temperate and subtropical regions.-Growth and flowering:Oenorthera biennis has a life span...
seeds, Helianthus annuus seed, Lablab purpureus,Nasturtium officinale and Psophocarpus tetragonolobus seed and leaf.
Use as a dietary supplement
There is evidence that blood tryptophan levels are unlikely to be altered by changing the diet, but for some time, tryptophan has been available in health food stores as a dietary supplementDietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
. Many people found tryptophan to be a safe and reasonably effective sleep aid, probably due to its ability to increase brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
levels of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(a calming neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
when present in moderate levels) and/or melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
(a sleep-inducing hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
secreted by the pineal gland
Pineal gland
The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...
in response to darkness or low light levels).
Clinical research has shown mixed results with respect to tryptophan's effectiveness as a sleep aid
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
, especially in normal patients. Furthermore tryptophan has shown some effectiveness for treatment of a variety of other conditions typically associated with low serotonin levels in the brain such as premenstrual dysphoric disorder
Premenstrual dysphoric disorder
Premenstrual dysphoric disorder is a severe form of premenstrual syndrome, afflicting 3% to 8% of women. It is a diagnosis associated primarily with the luteal phase of the menstrual cycle...
and seasonal affective disorder
Seasonal affective disorder
Seasonal affective disorder , also known as winter depression, winter blues, summer depression, summer blues, or seasonal depression, is a mood disorder in which people who have normal mental health throughout most of the year experience depressive symptoms in the winter or summer, spring or autumn...
. In particular, tryptophan has shown considerable promise as an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
alone and as an "augmenter" of antidepressant drugs. However, the reliability of these clinical trials has been questioned.
Metabolites
A metabolite of tryptophan, 5-Hydroxytryptophan5-Hydroxytryptophan
5-Hydroxytryptophan , also known as oxitriptan , is a naturally occurring amino acid and chemical precursor as well as metabolic intermediate in the biosynthesis of the neurotransmitters serotonin and melatonin from tryptophan....
(5-HTP), has been suggested as a treatment for epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
and depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, although clinical trials are regarded inconclusive and lacking. Since 5-HTP readily crosses the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and in addition is rapidly decarboxylated
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
to serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(5-hydroxytryptamine or 5-HT), it may be useful for the treatment of depression. However, serotonin has a relatively short half-life since it is rapidly metabolized by monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
.
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. As 5-HTP is usually converted to serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
before it can reach the brain, elevating blood serotonin levels greatly, it may cause diarrhea and heart problems, while only slightly increasing brain serotonin. In Europe, 5-HTP is prescribed with Carbidopa
Carbidopa
Carbidopa is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa.- Pharmacology :...
to delay the conversion of 5-HTP into serotonin until it reaches the brain (5-HTP is more effectively used when in conjunction with a dopa decarboxylase inhibitor such as Carbidopa
Carbidopa
Carbidopa is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa.- Pharmacology :...
, which slows its conversion to serotonin, allowing more of the supplement to reach the brain).
It is marketed in Europe for depression and other indications under the brand names Cincofarm, Tript-OH and Optimax (UK). 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 there is now a guarantee that the label accurately depicts what the bottle contains.
Tryptophan supplements and EMS
There was a large tryptophan-related outbreak of eosinophilia-myalgia syndromeEosinophilia-myalgia syndrome
Eosinophilia–myalgia syndrome is an incurable and sometimes fatal flu-like neurological condition that is believed to have been caused by ingestion of poorly produced L-tryptophan supplements...
(EMS
Eosinophilia-myalgia syndrome
Eosinophilia–myalgia syndrome is an incurable and sometimes fatal flu-like neurological condition that is believed to have been caused by ingestion of poorly produced L-tryptophan supplements...
) 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
Showa Denko
is a leading Japanese chemical engineering firm.Formed in 1939 by the merger of Nihon Electrical Industries and Showa Fertilizers, Showa Denko K.K. manufactures chemical products and industrial materials. SDK's products serve a wide array of fields ranging from heavy industry to the electronic...
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
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, 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 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 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
Pharmacy
Pharmacy is the health profession that links the health sciences with the chemical sciences and it is charged with ensuring the safe and effective use of pharmaceutical drugs...
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 psychiatrist
Psychiatrist
A psychiatrist is a physician who specializes in the diagnosis and treatment of mental disorders. All psychiatrists are trained in diagnostic evaluation and in psychotherapy...
s continue to prescribe, in particular as an augmenting agent for people unresponsive to antidepressant drugs.
Turkey meat and drowsiness
One belief is that heavy consumption of turkey meat (as for example in a ThanksgivingThanksgiving
Thanksgiving Day is a holiday celebrated primarily in the United States and Canada. Thanksgiving is celebrated each year on the second Monday of October in Canada and on the fourth Thursday of November in the United States. In Canada, Thanksgiving falls on the same day as Columbus Day in the...
or Christmas
Christmas
Christmas or Christmas Day is an annual holiday generally celebrated on December 25 by billions of people around the world. It is a Christian feast that commemorates the birth of Jesus Christ, liturgically closing the Advent season and initiating the season of Christmastide, which lasts twelve days...
feast) results in drowsiness
Somnolence
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
, which has been attributed to high levels of tryptophan contained in turkey. However, while turkey does contain high levels of tryptophan, the amount is comparable to that contained in most other meats.
Furthermore, post-meal drowsiness on Thanksgiving may have more to do with what else is consumed along with the turkey and, in particular, carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s. It has been demonstrated in both animal models and humans that ingestion of a meal rich in carbohydrates triggers release of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
. Insulin in turn stimulates the uptake of large neutral branched-chain amino acids
Branched-chain amino acids
A branched-chain amino acid is an amino acid having aliphatic side-chains with a branch...
(BCAA), but not tryptophan (an aromatic amino acid) into muscle, increasing the ratio of tryptophan to BCAA in the blood stream. The resulting increased ratio of tryptophan to BCAA in the blood reduces competition at the large neutral amino acid transporter (which transports both BCAA and aromatic amino acids), resulting in the uptake of tryptophan across the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
into the cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
(CSF). Once in the CSF, tryptophan is converted into serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
in the raphe nuclei
Raphe nuclei
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...
by the normal enzymatic pathway. The resultant serotonin is further metabolised into melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
by the pineal gland
Pineal gland
The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...
. Hence, this data suggest that "feast-induced drowsiness"—and, in particular, the common post-Christmas and North 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.
Aging
Rats fed a low tryptophan diet showed reduced blood levels of triiodothyronineTriiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....
, which was suggested to retard the aging process. Rats on tryptophan-reduced diets have shown increased maximum life span
Maximum life span
Maximum life span is a measure of the maximum amount of time one or more members of a population has been observed to survive between birth and death.Most living species have at least one upper limit on the number of times cells can divide...
and improved biomarkers of aging (although the rate of initial deaths was higher than in controls). The result was attributed to harmful effects of the age-related increase in brain serotonin.