Biogenic amines are the amines found in the biological system with many vital functions and roles. First, let me describe what is an amine. Amines are organic compounds containing an amino group as a functional group. They are basically considered as a derivative of ammonia in which one or more than one hydrogen atom is replaced by a substituent and therefore amines can be primary, secondary, and tertiary depending on the number of substituents. Amines can be alkyl or aryl depending on the type of substituent attached. There are some of the most important biogenic amines in our system that are playing a vital role in various physiological and metabolic processes as described below.
Histamine
Histamine is one of the most important biogenic amines that is involved in the local immune response to various allergens. It is synthesized from the histidine by the action of L-histidine decarboxylase. After synthesis, histamine can either be stored in the form of granules inside the mast cells and basophils or can be rapidly inactivated by histamine-N-methyltransferase. Histamine is primarily an immunologically active compound but it also acts as a neurotransmitter in the brain and central nervous system where it is secreted from the non-mast cells. It acts via the G-protein-linked cell surface receptors (Histamine receptor H1 to H4).
Histamine-activated G-protein linked cell surface receptor activates the G protein that initiates the signaling cascade via phospholipase C and the phosphatidylinositol pathway controlling the expression of the transcription factor, NF-κB, responsible for the inflammation processes. Therefore, antihistamines act on the receptor and stop the expression of the transcription factor responsible for the inflammation.
During the inflammatory responses mediated by different allergens and pathogens, immune cells such as basophils, release histamine in a large amount that leads to the hypersensitivity reaction. The symptoms may include redness of the skin and etching. Besides the immunological action, histamine plays several other roles such as vasodilation, lowering of blood pressure, gastric acid release, sleep-wake regulation, schizophrenia, multiple sclerosis, etc.
Serotonin
Serotonin, which is also called 5-hydroxytryptamine (5-HT), is a biogenic amine derived from L-tryptophan. It is a potent neurotransmitter best known for its contribution to feelings of being happy and loving. About 90 % of the serotonin is secreted in the enterochromaffin cells of the gastrointestinal tract where it regulates intestinal movement. The rest of the serotonin is secreted by the serotonergic neurons of the central nervous system where it has many other functions including the regulation of mood, sleep, and appetite.
Serotonin secreted by the enterochromaffin cells into the gastrointestinal tract is finally absorbed by blood platelets. Platelets release the serotonin once they bind to a clot where serotonin serves as a vasoconstrictor thereby regulating homeostasis and the blood clotting mechanism.
Serotonin is synthesized from L-tryptophan in a series of reactions catalyzed by enzymes. L-tryptophan is first converted into 5-Hydroxy-L-Tryptophan (5-HTP) catalyzed by tryptophan hydroxylase. In the next step, 5-HTP is converted into serotonin catalyzed by aromatic L-amino acid decarboxylase. Serotonin exerts its effects via the 5-HT receptors. These receptors are the G-protein-linked cell surface receptors located in the neurons of the central and peripheral nervous systems. The activated 5-HT receptors initiate a series of downstream signaling cascades leading to the expression of various enzymes responsible for the synthesis of other neurotransmitters.
Dopamine
Dopamine is another type of amine belonging to the class of biogenic amines. The full name of dopamine is 3,4-dihydroxyphenethylamine. It is a primary aromatic amine that is derived from L-tyrosine. In neurons and cells of the adrenal gland, L-tyrosine is converted to the L-DOPA (L-dihydroxyphenylalanine) catalyzed by the L-tyrosine hydroxylase. L-DOPA is the direct precursor of dopamine. The formation of dopamine from L-DOPA is catalyzed by the DOPA decarboxylase. This is the rate-limiting step of dopamine biosynthesis as well as other related products such as epinephrine and norepinephrine.
In the brain, dopamine acts as a neurotransmitter transmitting signals from one neuron to another. It is one of the three hormones (neuromodulatory hormones) that in coordination with one another controls depression, love, and happiness. Other functions of dopamine outside of the central nervous system include chemical messenger and vasodilator. It inhibits the release of norepinephrine in blood vessels and promotes the excretion of sodium and urine output while it decreases the production of insulin and gastrointestinal mobility.
Dopamine acts via the dopamine receptor (which are 5 types D1 to D5). These dopamine receptors belong to the G-protein-linked cell-surface receptor superfamily in which the cell-surface receptor is activated when the ligand binds to the respective receptor. After synthesis, dopamine is transported from the cytosol to the synaptic vesicles via solute carriers. In the synaptic cleft, these vesicles release dopamine into the synapse where it binds to the dopamine receptors and initiates the signaling cascade leading to the expression of neuromodulatory proteins.
Some diseases such as psychosis, schizophrenia, and Parkinson’s disease are related to the overproduction of dopamine and are often treated with drugs that interfere with either the production of dopamine or the activation of the dopamine receptor by dopamine.
Norepinephrine and epinephrine
Norepinephrine or noradrenaline and epinephrine or adrenaline are another set of biogenic amines derived from dopamine. They are also neuromodulatory hormones that act as neurotransmitters as well as hormones. Norepinephrine is derived from L-tyrosine. In the adrenal medulla and postganglionic neurons of the sympathetic nervous system, Norepinephrine is synthesized from L-tyrosine through a series of enzymatic reactions. However, its direct precursor is dopamine. Dopamine is converted to norepinephrine catalyzed by the dopamine β-monooxygenase. Norepinephrine may further be converted to epinephrine, another hormone catalyzed by phenylethanolamine N-methyltransferase.
Norepinephrine is mainly responsible for energy homeostasis. It is an energy metabolism-related hormone that is secreted at a high level during stress or danger and therefore it is known for the fight-or-flight response. It acts via the noradrenergic receptors (which are also called adrenergic receptors belonging to the G protein-linked cell surface receptors). There are two types of adrenergic receptors; alpha and beta and they mainly pass the downstream signal via the adenylate cyclase and cAMP signaling cascade.
In the brain (neuromodulatory effect), it increases alertness, and enhances the formation and retrieval of memory, it causes focused attention and restlessness while in the rest of the body (hormonal effect), it enhances the production of glucagon promotes the glucose catabolism, increased blood pressure, heart rate, etc.
So, these are some of the most important biogenic amines that play vital roles in the physiological and metabolic processes as well as in neuromodulatory processes.
