Biosynthesis, biodegradation and function of the most important biogenic amines and catecholamines
All biogenic amines and catecholamines are formed by the conversion of amino acids.
The basic biogenic amines include catecholamines (dopamine, adrenaline, noradrenaline), histamine, serotonin, melatonin, GABA, ethanolamine and its derivatives (acetylcholine, cysteamine, β-alanine and tryptamine).
Biogenic amines[edit | edit source]
A biogenic amine is a biogenic substance with one or more amine groups. They are basic nitrogenous compounds formed mainly by decarboxylation of amino acids or by amination and transamination of aldehydes and ketones
Histamine[edit | edit source]
Histamine is a chemical mediator that regulates a large number of cellular responses. It is involved in allergic and inflammatory (inflammatory) reactions and it is a strong vasodilator. It is also involved in secretion of HCl in the stomach and also serves as a neurotransmitter in a certain part of the brain.
It is synthesized by decarboxylation of histidine by histamine decarboxylase, which requires the presence of pyridoxal phosphate (PLP). Once it is synthesized, it is either stored in the granules of mast cells and basophils, from where it is released under the influence of various stimuli (radiation, allergen, drugs,...), or rapidly degraded by degradation enzymes – histamine-N-methyltransferase (mainly in the CNS) or diamine oxidase (also in other tissues).
Serotonin[edit | edit source]
Serotonin (also 5-hydroxytryptamine – 5HT) is synthesized and stored in various parts of the body - the largest amount of serotonin has been found in the intestinal mucosa. Smaller amounts are found in the CNS, where it plays the role of a neurotransmitter, and also in platelets.
It is synthesized from tryptophan by hydroxylation using tryptophan hydroxylase in the presence of tetrohydropterin (analogous to phenylalanine metabolism). The product of this reaction, 5-hydroxytryptophan, is subsequently decarboxylated by decarboxylase in the presence of PLP to serotonin. It is degraded by the enzyme monoamine oxidase (MAO).
Serotonin has several physiological functions such as pain perception, regulation of sleep, appetite, body temperature, blood pressure, cognitive functions and mood (causes a feeling of joy).
Melatonin[edit | edit source]
Melatonin is a hormone that is produced in the pineal gland from serotonin by acetylation and subsequent methylation. The stimulus for synthesis is mainly light (especially the blue component).
It regulates the circadian rhythm, also is an antioxidant and plays a role in immunity and smooth muscle regulation.
Tryptamine[edit | edit source]
Tryptamine is produced by decarboxylation of tryptophan. It is a regulatory molecule, the function of which is still little known.
GABA[edit | edit source]
GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the CNS.
It is formed by the decarboxylation of glutamate by the enzyme glutamate decarboxylase in the presence of PLP. GABA is gradually degraded to succinate, which can enter the citrate cycle.
Cystamine[edit | edit source]
Cystamine is part of coenzyme A, which is formed by the decarboxylation of cysteine. β-alanine is formed by the decarboxylation of aspartate, but is also formed during the breakdown of pyrimidine bases.
Ethanolamine[edit | edit source]
Ethanolamine is formed by the decarboxylation of serine. Subsequent triple methylation produces choline, which is a precursor of acetylcholine.
The enzyme choline acetyltransferase catalyzes the formation of acetylcholine from acetyl-CoA and choline. Ethanolamine and choline are part of phospholipids – phosphatidylcholine and phosphatidylethanolamine.
Acetylcholine acts as a neurotransmitter.
Catecholamines[edit | edit source]
Dopamine, noradrenaline and adrenaline are biologically active (biogenic) amines, collectively called catecholamines.
Dopamine and noradrenaline are synthesized in the brain and function as neurotransmitters. Adrenaline and noradrenaline are also synthesized in the adrenal medulla.
Noradrenaline and adrenaline are released from storage vesicles in the adrenal medulla in response to fear, stress, cold and low blood glucose levels. Outside the NS, noradrenaline and its methylated derivative, adrenaline, act as hormones regulating carbohydrate and lipid metabolism, increasing the degradation of glycogen and triacylglycerols and also increase blood pressure and cardiac output.These effects are part of a coordinated response that prepares the individual for stress - the "fight-or-flight" response.
Synthesis[edit | edit source]
Catecholamines are synthesized from tyrosine which is first hydroxylated by tyrosine hydroxylase to form 3,4-dihydroxyphenylalanine (DOPA) in a reaction that is analogous to the hydroxylation of phenylalanine. Tetrahydrobiopterin (BH4) – a key enzyme widespread in the CNS, sympathetic ganglia and adrenal medulla – represents one of the main regulatory steps of this pathway.
DOPA is decarboxylated in a reaction requiring pyridoxal phosphate (PLP) to form dopamine, which is hydroxylated by dopamine β-hydroxylase to form noradrenaline in a reaction requiring vitamin C (ascorbate) and copper. Epinephrine is formed from noradrenaline by N-methylation using S-adenosylmethionine (SAM) as a methyl donor.
Degradation[edit | edit source]
Degradation of catecholamines begins with their inactivation by oxidative deamination catalyzed by monoamine oxidase (MAO) or by O-methylation catalyzed by catechol-O-methyltransferase (COMT), which uses SAM as a methyl donor. Both reactions cannot occur simultaneously.
The aldehyde products of the MAO reaction are oxidized to the corresponding acids. The metabolic products of these reactions are then excreted in the urine as vanillylmandelic acid (VMA) formed from noradrenaline and adrenaline, and as homovanillic acid formed from dopamine.
Increased concentration of VMA occurs in pheochromocytomas, tumors of the kidneys accompanied by excessive production of catecholamines.
MAO is an enzyme found in nervous and other tissues, such as the intestine or liver. In the neuron it oxidatively deamines and inactivates any excess neurotransmitters (noradrenaline, dopamine, serotonin) that can escape from synaptic vesicles while the neuron is at rest.
MAO inhibitors can reversibly or irreversibly inactivate the enzyme, allowing neurotransmitter molecules to escape degradation and thus simultaneously accumulate in the presynaptic neuron and also leak into the synaptic space. This causes activation of noradrenaline and serotonin receptors, which may result in the antidepressant effects of these drugs.
Sources[edit | edit source]
MATOUŠ, Bohuslav, et al. Základy lékařské chemie a biochemie. 1. vydání. Praha : Galén, 2010. 540 s.
