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Biogenic Amines

For medical students2 min readUpdated 2026-10-10

Biogenic amines are biologically active substances formed in the body by the removal of an alpha-carboxyl group from amino acids. They perform vital physiological functions, acting as neurotransmitters, hormones, and local regulators.

Primary reactionDecarboxylation (removal of CO2 from an amino acid)

Main cofactorPyridoxal phosphate (PLP) — the active form of vitamin B6

Key mediatorGABA is the primary inhibitory neurotransmitter of the higher CNS

Excretion pathwayAmine oxidation products (acids) are cleared by the kidneys

Mechanism of Formation and Classification

The synthesis of biogenic amines occurs via decarboxylation—the removal of the $\alpha$-carboxyl group from a parent amino acid or its derivative. The reaction proceeds with the release of carbon dioxide ($CO_2$). Enzymes known as decarboxylases catalyze this process, requiring pyridoxal phosphate (PLP) as a coenzyme.

Based on their biological functions, biogenic amines are divided into three main groups:

Neurotransmitters (ensure nerve impulse transmission) — serotonin, dopamine, GABA.
Hormones (regulate systemic processes) — epinephrine (synthesized in the adrenal medulla).
Local regulators (tissue hormones) — histamine.

Gamma-Aminobutyric Acid (GABA)

GABA is synthesized in neurons and serves as the principal inhibitory neurotransmitter in the central nervous system.

The precursor of GABA is glutamate (glutamic acid). Catalyzed by glutamate decarboxylase using PLP as a cofactor, $CO_2$ is cleaved from glutamate to yield GABA.

In clinical practice, GABA-derived medications are used for traumatic brain injuries, intellectual disability, cerebrovascular disorders, and endogenous depressions.

Acetylcholine Synthesis

Acetylcholine is also classified as a biogenic amine, and its formation in nervous tissue occurs in several steps:

First, the amino acid serine undergoes decarboxylation (catalyzed by serine decarboxylase with the PLP cofactor) to form ethanolamine.
Next, ethanolamine is methylated by ethanolaminemethyltransferase. The methyl group donor is SAM (S-adenosylmethionine), resulting in choline formation.
In the final step, choline acetyltransferase combines choline and Acetyl-CoA to form acetylcholine.

Important: Impaired acetylcholine synthesis at neuromuscular junctions leads to a severe pathology known as myasthenia gravis (marked muscle weakness).

Serotonin Metabolism

Serotonin is a neurotransmitter of neural pathways, often referred to as the "pleasure hormone." It is synthesized in the hypothalamus, adrenal glands, and mast cells.

The starting substrate is the amino acid tryptophan. The process takes place in two steps:

Hydroxylation of tryptophan using oxygen and tetrahydrobiopterin ($H_4 ext{BH}_4$) to form 5-hydroxytryptophan.
Decarboxylation of the resulting product to yield serotonin.

Serotonin exerts diverse physiological effects: it regulates blood pressure, body temperature, and respiration, constricts blood vessels, stimulates smooth muscle contraction, and enhances gut motility. It is also released from mast cells, participating in allergic reactions.

Inactivation of Biogenic Amines

To prevent the continuous action of biogenic amines, the body must inactivate them. This occurs via two main pathways:

1. Methylation Typical for histamine, epinephrine, and norepinephrine. The reaction is catalyzed by methyltransferases, with SAM serving as the methyl group donor. For example, epinephrine is converted to metanephrine by replacing the hydrogen of the ring hydroxyl group with a methyl radical (-O-$CH_3$).

2. Oxidative Deamination Typical for dopamine, serotonin, GABA, and norepinephrine. This is mediated by monoamine oxidases (MAO) with an FAD cofactor. The biogenic amine loses ammonia ($NH_3$), converts into an aldehyde, and is subsequently oxidized to an acid. These acids are ultimately excreted by the kidneys.

Note: GABA can also be inactivated via an alternative pathway—transamination to succinate, which is then oxidized in the tricarboxylic acid (TCA) cycle.

Mnemonic

To easily recall the precursor amino acids of major neurotransmitters, use paired associations: GABA from Glutamate (G-G), Serotonin from Tryptophan (S-T), Acetylcholine from Serine (A-S).

Frequently asked questions

From which amino acid and with the help of which enzyme is histamine synthesized?

Histamine is synthesized from the amino acid histidine by the enzyme histidine decarboxylase.

The synthesis process has the following characteristics:

Synthesis reaction — decarboxylation of histidine, releasing carbon dioxide ($CO_2$).
Reaction cofactor — pyridoxal phosphate (PLP, vitamin $B_6$).
Localization — synthesis occurs in mast cells of connective tissue, basophils, gastric mucosal cells, and neurons.

The resulting biogenic amine functions as a mediator of inflammation and allergic reactions, and acts as a digestive hormone and neurotransmitter.

What are the steps and enzymes for synthesizing catecholamines (dopamine, norepinephrine, epinephrine) from tyrosine?

The synthesis of catecholamines from tyrosine occurs in four steps involving specific enzymes.

Step 1 (Tyrosine → DOPA) — catalyzed by tyrosine hydroxylase (cofactors: $H_4 ext{BH}_4$, $Fe^{2+}$, $O_2$).
Step 2 (DOPA → Dopamine) — catalyzed by DOPA decarboxylase (cofactor: PLP, $CO_2$ released).
Step 3 (Dopamine → Norepinephrine) — catalyzed by dopamine $eta$-hydroxylase (cofactors: vitamin C, $O_2$).
Step 4 (Norepinephrine → Epinephrine) — catalyzed by phenylethanolamine N-methyltransferase, where SAM (S-adenosylmethionine) serves as the methyl group donor.

Which cofactors are required for the two steps of serotonin synthesis from tryptophan?

Tetrahydrobiopterin and pyridoxal phosphate are required as cofactors for the two steps of serotonin synthesis from tryptophan.

First step (hydroxylation) — conversion of tryptophan to 5-hydroxytryptophan mediated by tryptophan hydroxylase. The cofactor for this reaction is tetrahydrobiopterin ($H_4 ext{BH}_4$).
Second step (decarboxylation) — conversion of 5-hydroxytryptophan to serotonin by aromatic L-amino acid decarboxylase. The cofactor for this enzyme is pyridoxal phosphate (PLP, vitamin B6).

Which amino acid gives rise to dopamine and norepinephrine?

Dopamine, norepinephrine, and epinephrine 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 abolishing its activity.

Why is SAM required in methylation reactions?

SAM (S-adenosylmethionine) acts as a universal methyl group donor. After donating the methyl group, it is converted into SAH (S-adenosylhomocysteine).

Go deeper

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) transformations