The starting material for thousands of different amines is ammonia (NH3), in which the hydrogen atoms are successively replaced by alkyl groups or by aryl groups with at least one aromatic six-membered ring backbone. Biogenic amines are formed by decarboxylation of amino acids. They are directly metabolically active or part of a complex enzyme or hormone or form the precursors for a variety of hormones, enzymes, neurotransmitters, and alkaloids.
What are amines?
The basic substance for the formation of amines is ammonia (NH3). Substitution of one, two, or all three hydrogen atoms by alkyl or aryl groups produces primary, secondary, or tertiary amines. Alkyl groups are aliphatic hydrocarbon chains defined by the general molecular formula CnH2n+1. The simplest form is the methyl group with the molecular formula -CH3. Aryl groups consist of an organic radical with at least one aromatic six-membered ring as the basic skeleton. The phenyl radical (-C6H5) forms the simplest aryl group. However, biogenic amines are not newly synthesized on the basis of an ammonia derivative, but are obtained by decarboxylation of amino acids, the removal of the carboxyl group (-COOH) with the elimination of a carbon dioxide molecule. Alternatively, biogenic amines can be ingested directly with food and absorbed in the small intestine (ileum). Biogenic amines such as beta-alanine and cysteamine are components of certain coenzymes or function as neurotransmitters such as alpha-amino-butyric acid, dopamine, serotonin and norepinephrine. Other amines form the precursors to cobalamins (vitamin B12), catecholamines, a variety of alkaloids, and many other bioactive substances.
Function, effects, and roles
A tremendous variety of biogenic amines are involved in very many metabolic processes as neurotransmitters or part of enzymes or hormones. On the other hand, amines also exert an indirect influence on the body’s metabolism as precursors for a number of other hormones, enzymes, neurotransmitters, and alkaloids. A certain special role is played by the biogenic amine phenethylamine (PEA). Biochemically, it is a precursor for the synthesis of catecholamines such as adrenaline and dopamine. PEA exerts a stimulatory effect on metabolism similar to that of the sympathetic nervous system. Blood pressure and blood glucose levels increase and respiratory rate increases. The body’s tolerance to PEA varies greatly from individual to individual. The influence ranges from slightly stimulating to toxic effects. The multitude of functions and tasks indicates that the concentration of specific amines, which are directly involved in control functions of the metabolism, must be sensitively monitored and controlled. This is especially true for exogenously ingested amines, whose accumulation in the body depends on the randomness of food intake. The resulting potential problems are counteracted by enzymes such as oxidases, methyltransferases and other catabolic enzymes. The catabolic enzymes, each specialized in inhibiting specific amines, prevent excessive increases in the concentration of neurotransmitters and other immediate-acting amines. In turn, to prevent too much inhibition of the catabolic enzymes, specific amines act as inhibitors of the catabolically active enzymes. For example, the biogenic amine tyramine, a neurotransmitter that the body obtains from tyrosine by decarboxylation, acts as an inhibitor of diaminooxidase (DAO) and histamine N-methyltransferase (HNMT). Tyramine thus prevents histamine from being broken down too quickly.
Formation, occurrence, properties, and optimal levels
The almost incalculable variety of simple to complex biogenic amines are produced in the body by enzymatic-catalytic conversion of amino acids or ingested with food and absorbed in the small intestine. Biogenic amines, which usually have a slightly alkaline effect in the body, are present in low concentrations in many foods such as meat, fish, milk and dairy products, as well as in various vegetables. Since amines are often synthesized by microbes, the content of biogenic amines, especially histamine, is particularly high in fermented foods such as sauerkraut, beer and wine, as well as in certain (mature) cheeses and meat products, which can lead to an oversupply. Some people react to this with skin redness, itching, nausea, migraines and circulatory problems.These are not allergic symptoms, but overreactions to an excess of histamine. Histamine is an important messenger and stimulant of the immune system. As a tissue hormone, histamine, which can also be formed from the amino acid histidine, is involved in all inflammatory reactions. An optimal concentration of biogenic amines in the body cannot be defined, as the requirement is situation-dependent due to their diverse manifestations and functions.
Diseases and disorders
The very diverse tasks and functions of amines, which are often associated with chains of sequential enzymatic-catalytically controlled biochemical reactions in intermediate metabolism, mean that disorders can also occur. Frequently, the disturbances lead to symptoms and complaints that are unspecific and only allow conclusions to be drawn about specific problems when certain symptoms occur simultaneously. An example of an indication of deficient supply of certain monoamines such as norepinephrine, serotonin and other neurotransmitters, are symptoms such as fatigue, lack of drive and depressive moods. The underlying deficiency of certain neurotransmitters and hormones may be due to an actual undersupply or to impaired receptor function. Decreased receptor activity may occur, for example, as an undesirable side effect of medications or may be caused by certain toxins. In both cases, the therapeutic goal is to increase the supply of the corresponding biogenic amines. An opposite situation, an oversupply of biogenic amines, can also be triggered by a gene mutation that causes a deficiency of mono- or diaminooxidase enzymes. Substances such as norepinephrine, serotonin and others can then not be metabolized to the required extent, which can lead to allergy-like symptoms. Certain foods or substances can enhance or weaken the effect of biogenic amines. For example, alcohol consumption increases the effect of amines.
