Mechanism of formation and classification
The synthesis of biogenic amines occurs via decarboxylation — the removal of the $\alpha$-carboxyl group from the parent amino acid or its derivative. The reaction proceeds with the release of carbon dioxide ($CO_2$). Enzymes known as decarboxylases participate in this process, requiring the coenzyme pyridoxal phosphate (PLP) to function.
Based on their biological functions, biogenic amines are divided into three main groups:
- Neurotransmitters (ensure the transmission of nerve impulses) — serotonin, dopamine, GABA.
- Hormones (regulate systemic processes) — adrenaline (synthesized in the adrenal medulla).
- Local regulators (tissue hormones) — histamine.
Gamma-aminobutyric acid (GABA)
GABA is synthesized in nerve cells and serves as the primary inhibitory neurotransmitter in the central nervous system.
The precursor of GABA is glutamate (glutamic acid). Under the action of the enzyme glutamate decarboxylase and the coenzyme PLP, $CO_2$ is cleaved from glutamate, forming GABA.
In clinical practice, GABA-based drugs (such as Gamalate and Aminalon) are widely used. They are prescribed to patients with brain injuries, mental retardation, cerebral circulation disorders, and endogenous depressions.
Acetylcholine synthesis
Acetylcholine also belongs to biogenic amines, and its formation takes place in nervous tissue in several stages:
- First, the amino acid serine undergoes decarboxylation (catalyzed by serine decarboxylase with the coenzyme PLP) to ethanolamine.
- Next, ethanolamine is methylated with the help of ethanolamine methyltransferase. The methyl group donor is SAM (S-adenosylmethionine). Choline is formed as a result.
- At the final stage, choline acetyltransferase combines choline and Acetyl-CoA to form acetylcholine.
Important: a disruption in acetylcholine synthesis in synapses leads to a severe pathology known as myasthenia gravis (pronounced muscle weakness).
Serotonin metabolism
Serotonin is a neurotransmitter of conducting pathways, often referred to as the «pleasure hormone». It is synthesized in the hypothalamus, adrenal glands, and mast cells.
The initial substrate is the amino acid tryptophan. The process proceeds in two steps:
- Hydroxylation of tryptophan involving oxygen and tetrahydrobiopterin ($H_4BP$) to 5-hydroxytryptophan.
- Decarboxylation of the resulting product to serotonin.
Serotonin exerts numerous physiological effects: it regulates blood pressure, body temperature, and respiration, constricts blood vessels, stimulates smooth muscle contraction, and enhances intestinal peristalsis. It is also released from mast cells, participating in allergic reactions.
Inactivation of biogenic amines
To prevent the action of biogenic amines from being endless, the body must inactivate them. This occurs via two pathways:
1. Methylation Characteristic of histamine, adrenaline, and noradrenaline. The reaction is catalyzed by methyltransferases, with SAM donating the methyl group. For example, adrenaline is converted into metanephrine by replacing the hydrogen of the hydroxyl group in the ring with a methyl radical (-O-$CH_3$).
2. Oxidative deamination Characteristic of dopamine, serotonin, GABA, and noradrenaline. The enzymes involved are monoamine oxidases (MAO) with the coenzyme FAD. The biogenic amine loses ammonia ($NH_3$), converts into an aldehyde, and is subsequently oxidized to an acid. These acids are ultimately simply excreted by the kidneys.
Note: GABA can also be inactivated through another pathway — transamination to succinate, which is then oxidized in the tricarboxylic acid cycle (Krebs cycle).
Briefly: answers to topical questions
From which amino acid and with the help of which enzyme is histamine synthesized?
Histamine is synthesized from the amino acid histidine with the help of the enzyme histidine decarboxylase.
The process of histamine formation includes the following characteristics:
- Synthesis reaction — decarboxylation of histidine, resulting in the release of carbon dioxide ($CO_2$).
- Reaction coenzyme — pyridoxal phosphate (PLP, vitamin $B_6$).
- Localization of the process — synthesis occurs in mast cells of connective tissue, basophils, gastric cells, and neurons.
The resulting biogenic amine functions as a mediator of inflammation and allergic reactions, and also acts as a digestive hormone and neurotransmitter.
What are the stages and enzymes involved in the synthesis of catecholamines (dopamine, noradrenaline, adrenaline) from tyrosine?
The synthesis of catecholamines from tyrosine occurs in four stages involving specific enzymes.
- Stage 1 (Tyrosine → DOPA) — catalyzed by the enzyme tyrosine hydroxylase (cofactors: $H_4BP$, $Fe^{2+}$, $O_2$).
- Stage 2 (DOPA → Dopamine) — catalyzed by the enzyme DOPA decarboxylase (cofactor: PLP, $CO_2$ is released).
- Stage 3 (Dopamine → Noradrenaline) — catalyzed by the enzyme dopamine beta-hydroxylase (cofactors: vitamin C, $O_2$).
- Stage 4 (Noradrenaline → Adrenaline) — catalyzed by the enzyme methyltransferase, where the methyl group donor is SAM (S-adenosylmethionine).
Which coenzymes are required for the two steps of serotonin synthesis from tryptophan?
The two steps of serotonin synthesis from tryptophan require the coenzymes tetrahydrobiopterin and pyridoxal phosphate.
- First step (hydroxylation) — conversion of tryptophan to 5-hydroxytryptophan involving the enzyme tryptophan hydroxylase. The coenzyme in this reaction is tetrahydrobiopterin ($H_4$BP).
- Second step (decarboxylation) — conversion of 5-hydroxytryptophan to serotonin under the action of aromatic L-amino acid decarboxylase. The coenzyme for this enzyme is pyridoxal phosphate (PLP, vitamin B6).
To easily remember the parent amino acids of the main neurotransmitters, use paired associations: GABA from Glutamate (G-G), Serotonin from Tryptophan (S-T), Acetylcholine from Serine (A-S).
Class and exam questions
Which amino acid is the precursor of dopamine and noradrenaline?
Dopamine, noradrenaline, and adrenaline belong to the catecholamine group. Their common precursor is the amino acid tyrosine.
What is the difference between MAO and methyltransferases?
These are enzymes of different inactivation pathways. MAO (monoamine oxidases) cleave ammonia and oxidize the amine to an acid, whereas methyltransferases attach a methyl group from SAM, altering the amine's structure and rendering it inactive.
Why is SAM required in methylation reactions?
SAM (S-adenosylmethionine) acts as a universal methyl group donor. Upon donating it, it is converted into SAH (S-adenosylhomocysteine).
What else to study on this topic
- Melanin synthesis in the skin
- Iodothyronine synthesis in the thyroid gland
- Detailed mechanism of oxidative deamination of biogenic amines
- Complete cycle of S-adenosylmethionine (SAM) conversions
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