Tyramine is a
naturally occurringNatural resources occur naturally within environments that exist relatively undisturbed by mankind, in a natural form. A natural resource is often characterized by amounts of biodiversity and geodiversity existent in various ecosystems....
monoamine
compoundA chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
and
trace amineTrace amines are endogenous compounds structurally related to classical biogenic amines, such as catecholamines, serotonin and histamine. Trace amines include p-tyramine, β-phenylethylamine, tryptamine, octopamine, and 3-iodothyronamine, and are found in the nervous systems of animals from insects...
derived from the
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
tyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
. Tyramine acts as a
catecholamineCatecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
(
dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
,
norepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline),
epinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(adrenaline))
releasing agentA releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...
. Notably, however, it is unable to cross the blood-brain-barrier (BBB), resulting in only non-psychoactive
peripheralA peripheral is a device attached to a host computer, but not part of it, and is more or less dependent on the host. It expands the host's capabilities, but does not form part of the core computer architecture....
sympathomimetic effects. When tyramine-rich foods are ingested in conjunction with a
monoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
(MAOI), tyramine is responsible for the so-called "cheese effect" sometimes seen with their use.
Tyramine is a
naturally occurringNatural resources occur naturally within environments that exist relatively undisturbed by mankind, in a natural form. A natural resource is often characterized by amounts of biodiversity and geodiversity existent in various ecosystems....
monoamine
compoundA chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
and
trace amineTrace amines are endogenous compounds structurally related to classical biogenic amines, such as catecholamines, serotonin and histamine. Trace amines include p-tyramine, β-phenylethylamine, tryptamine, octopamine, and 3-iodothyronamine, and are found in the nervous systems of animals from insects...
derived from the
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
tyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
. Tyramine acts as a
catecholamineCatecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
(
dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
,
norepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline),
epinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(adrenaline))
releasing agentA releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...
. Notably, however, it is unable to cross the blood-brain-barrier (BBB), resulting in only non-psychoactive
peripheralA peripheral is a device attached to a host computer, but not part of it, and is more or less dependent on the host. It expands the host's capabilities, but does not form part of the core computer architecture....
sympathomimetic effects. When tyramine-rich foods are ingested in conjunction with a
monoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
(MAOI), tyramine is responsible for the so-called "cheese effect" sometimes seen with their use.
Occurrence
Tyramine occurs widely in plants and
animalAnimals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s, and is metabolized by the
enzymeEnzymes 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...
monoamine oxidaseL-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...
. In foods, it is often produced by the
decarboxylationDecarboxylation 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...
of
tyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
during
fermentationFermentation in food processing typically is the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions. Fermentation in simple terms is the chemical conversion of sugars into ethanol...
or
decayDecomposition is the process by which organic material is broken down into simpler forms of matter. The process is essential for recycling the finite matter that occupies physical space in the biome. Bodies of living organisms begin to decompose shortly after death...
. Foods containing considerable amounts of tyramine include meats that are potentially spoiled or pickled, aged, smoked, fermented, or marinated (some
fishFish is a food consumed by many species, including humans. The word "fish" refers to both the animal and to the food prepared from it. Fish has been an important source of protein for humans throughout recorded history.-Terminology:...
,
poultryPoultry 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"...
, and
beefBeef is the culinary name for meat from bovines, especially domestic cattle. Beef can be harvested from cows, bulls, heifers or steers. It is one of the principal meats used in the cuisine of the Middle East , Australia, Argentina, Brazil, Europe and the United States, and is also important in...
); most
porkPork is the culinary name for meat from the domestic pig , which is eaten in many countries. It is one of the most commonly consumed meats worldwide, with evidence of pig husbandry dating back to 5000 BC....
(except
curedCuring refers to various food preservation and flavoring processes, especially of meat or fish, by the addition of a combination of salt, nitrates, nitrite or sugar. Many curing processes also involve smoking, the process of flavoring, or cooking...
hamHam is a cut of meat from the thigh of the hind leg of certain animals, especiallypigs. Nearly all hams sold today are fully cooked or cured.-Etymology:...
);
chocolateChocolate 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...
;
alcoholic beverageAn alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
s; and fermented foods, such as most
cheeseCheese is a generic term for a diverse group of milk-based food products. Cheese is produced throughout the world in wide-ranging flavors, textures, and forms....
s (except
ricottaRicotta is an Italian dairy product made from sheep milk whey left over from the production of cheese. Although typically referred to as ricotta cheese, ricotta is not properly a cheese because it is not produced by coagulation of casein...
,
cottage cheeseCottage 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...
,
cream cheeseCream cheese is a soft, mild-tasting, white cheese with a high fat content. Traditionally, it is made from unskimmed milk enriched with additional cream....
and neufchatel cheese),
sour cream Sour cream is a dairy product rich in fats obtained by fermenting a regular cream by certain kinds of lactic acid bacteria. The bacterial culture, which is introduced either deliberately or naturally, sours and thickens the cream. Its name stems from the production of lactic acid by bacterial...
, yogurt,
shrimp pasteShrimp paste or shrimp sauce, is a common ingredient used in Southeast Asian and Southern Chinese cuisine. It is known as terasi in Indonesian, ngapi in Burmese, kapi in Thai, Khmer and Lao language, belacan in Malay, mắm ruốc, mắm tép and mắm tôm in...
,
soy sauceSoy sauce is a condiment produced by fermenting soybeans with Aspergillus oryzae or Aspergillus sojae molds, along with water and salt...
, soy bean condiments, teriyaki sauce,
tofuis a food made by coagulating soy milk and then pressing the resulting curds into soft white blocks. It is part of East Asian and Southeast Asian cuisine such as Chinese, Japanese, Korean, Indonesian, Vietnamese, and others. There are many different varieties of tofu, including fresh tofu and tofu...
,
tempehTempeh , or tempe , is a traditional soy product originally from Indonesia. It is made by a natural culturing and controlled fermentation process that binds soybeans into a cake form, similar to a very firm vegetarian burger patty...
,
miso soupis a traditional Japanese soup consisting of a stock called "dashi" into which is mixed softened miso paste. Many ingredients are added depending on regional and seasonal recipes, and personal preference.-Miso paste:...
,
sauerkrautSauerkraut , directly translated from German: "sour cabbage", is finely shredded cabbage that has been fermented by various lactic acid bacteria, including Leuconostoc, Lactobacillus, and Pediococcus. It has a long shelf-life and a distinctive sour flavor, both of which result from the lactic acid...
,
broad (fava) beansThis article refers to the Broad Bean plant. For Broadbean the company, see Broadbean, Inc.Vicia faba, the Broad Bean, Fava Bean, Field Bean, Bell Bean or Tic Bean, is a species of bean native to north Africa and southwest Asia, and extensively cultivated elsewhere. A variety is provisionally...
, green bean pods, Italian flat (Romano)
beanBean is a common name for large plant seeds of several genera of the family Fabaceae used for human food or animal feed....
s,
snow peaThe snow pea is a legume, more specifically a variety of pea eaten whole in its pod while still unripe...
s,
avocadoThe avocado is a tree native to Central Mexico, classified in the flowering plant family Lauraceae along with cinnamon, camphor and bay laurel...
s,
bananaBanana is the common name for herbaceous plants of the genus Musa and for the fruit they produce. Bananas come in a variety of sizes and colors when ripe, including yellow, purple, and red....
s,
pineapplePineapple is the common name for a tropical plant and its edible fruit, which is actually a multiple fruit consisting of coalesced berries. It was given the name pineapple due to its resemblance to a pine cone. The pineapple is by far the most economically important plant in the Bromeliaceae...
, eggplants,
figFicus is a genus of about 850 species of woody trees, shrubs, vines, epiphytes, and hemiepiphyte in the family Moraceae. Collectively known as fig trees or figs, they are native throughout the tropics with a few species extending into the semi-warm temperate zone. The Common Fig Ficus is a genus of...
s, red
plumA plum or gage is a stone fruit tree in the genus Prunus, subgenus Prunus. The subgenus is distinguished from other subgenera in the shoots having a terminal bud and solitary side buds , the flowers in groups of one to five together on short stems, and the fruit having a groove running down one...
s,
raspberriesThe raspberry or hindberry is the edible fruit of a multitude of plant species in the genus Rubus, most of which are in the subgenus Idaeobatus; the name also applies to these plants themselves...
,
peanutThe 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,
Brazil nutThe Brazil nut is a South American tree in the family Lecythidaceae, and also the name of the tree's commercially harvested edible seed.- Order :...
s,
coconutThe coconut palm, Cocos nucifera, is a member of the family Arecaceae . It is the only accepted species in the genus Cocos. The term coconut can refer to the entire coconut palm, the seed, or the fruit, which is not a botanical nut. The spelling cocoanut is an old-fashioned form of the word...
s, processed meat,
yeastYeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
, and an array of
cacti-See also:* RRDtool The underlying software upon which Cacti is built* MRTG The original Multi Router Traffic Grapher from which RRDtool was "extracted".* Munin -External links:******...
.
Physical effects and pharmacology
Tyramine is physiologically metabolized by MAO
A. In
humanHumans are the only living species in the Homo genus...
s, if monoamine metabolism is compromised by the use of
monoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
s (MAOIs) and foods high in tyramine are ingested, a
hypertensive crisisMalignant hypertension or hypertensive emergency is severe hypertension with acute impairment of an organ system and the possibility of irreversible organ-damage...
can result, as tyramine can cause the release of stored monoamines, such as
dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
,
norepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and
epinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
. The first signs of this were discovered by a
neurologistA neurologist is a physician who specializes in neurology, and is trained to investigate, or diagnose and treat neurological disorders.Neurology is the medical specialty related to the human nervous system. The nervous system encompasses the brain, spinal cord, and peripheral nerves. A specialist...
who noticed his wife, who at the time was on MAOI medication, had severe headaches when eating cheese. For this reason, the crisis is still called the "cheese effect", though other foods can cause the same problem.. Most processed cheeses do not contain high enough tyramine to cause hypertensive effects, although some aged cheeses (such as Stilton cheese) do.
A large dietary intake of tyramine (or a dietary intake of tyramine while taking MAO inhibitors) can cause the tyramine pressor response, which is defined as an increase in systolic blood pressure of 30 mmHg or more. The displacement of norepinephrine (noradrenaline) from neuronal storage vesicles by acute tyramine ingestion is thought to cause the
vasoconstrictionVasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
and increased heart rate and blood pressure of the pressor response. In severe cases, adrenergic crisis can occur.
However, if one has had repeated exposure to tyramine, there is a decreased pressor response; tyramine is degraded to
octopamineOctopamine is an endogenous biogenic amine that is closely related to norepinephrine, and has effects on the adrenergic and dopaminergic systems. It is also found naturally in numerous plants, including bitter orange. Biosynthesis of the D--enantiomer of octopamine is by β-hydroxylation of...
, which is subsequently packaged in synaptic vesicles with norepinephrine (noradrenaline). Therefore, after repeated tyramine exposure, these vesicles contain an increased amount of octopamine and a relatively reduced amount of norepinephrine. When these vesicles are secreted upon tyramine ingestion, there is a decreased pressor response, as less norepinephrine is secreted into the
synapseIn the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, and octopamine does not activate alpha or beta adrenergic receptors.
When using a MAO inhibitor (MAOI), the intake of approximately 10 to 25 mg of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild reaction.
The possibility that tyramine acts directly as a
neurotransmitterNeurotransmitters 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...
was revealed by the discovery of a
G proteinG proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
-coupled receptor with high affinity for tyramine, called
TA1Trace amine-associated receptors, abbreviated TAAR and otherwise known as trace amine receptors, abbreviated TAR or TA, are a class of G protein-coupled receptors identified in 2001....
. The TA1 receptor is found in the
brainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
as well as peripheral tissues, including the
kidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
. The existence of a receptor with high affinity for tyramine supports the hypothesis that tyramine may also act directly to affect blood pressure regulation.
Dietary tyramine intake has also been associated with
migraineMigraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
in select populations, leading many sufferers to restrict foods high in tyramine.
Reports on the tyramine-migraine link have been both affirmed and denied. AT the Department of Neurology and EEG at the London Hospital, a double-blind study has shown that there is no significant relationship between tyramine ingestion and migraines. The EEG changes observed,however, do support that tyramine plays a role on the central nervous system in some subjects. A 2007 review published in Neurological Sciences
presented data showing migraine and cluster headaches are characterised by an increase
of circulating neurotransmitters and neuromodulators (including tyramine, octopamine and synephrine) in the hypothalamus, amygdala and dopaminergic system.
Biosynthesis
Biochemically, tyramine is produced by the
decarboxylationDecarboxylation 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...
of
tyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
via the action of the enzyme
tyrosine decarboxylaseIn enzymology, a tyrosine decarboxylase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, L-tyrosine, and two products, tyramine and carbon dioxide....
. Tyramine can in turn be converted to methylated
alkaloidAlkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
derivatives
N-methyltyramineN-Methyltyramine is a natural phenethylamine alkaloid found in a variety of plants. Biosynthetically, it is produced by the methylation of tyramine via the action of the enzyme tyramine N-methyltransferase....
,
N,N-dimethyltyramineHordenine is a phenethylamine alkaloid with antibacterial and antibiotic properties. It stimulates the release of norepinephrine in mammals, working as a stimulant...
(hordenine), and
N,
N,
N-trimethyltyramine (candicine).
Chemistry
In the laboratory, tyramine can be synthesized in various ways, in particular by the decarboxylation of tyrosine.