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Biogenic amine
Biogenic amine
Biogenic amine
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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. Biogenic amines are organic bases with low molecular weight and are synthesized by microbial, vegetable and animal metabolisms. In food and beverages they are formed by the enzymes of raw material or are generated by microbial decarboxylation of amino acids.[1]

List of notable biogenic amines

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Monoamines

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Part of this section is transcluded from Trace amine. (edit | history)

Some prominent examples of biogenic monoamines include:

Monoamine neurotransmitters

Trace amines (endogenous amines that activate the human TAAR1 receptor)

Tryptamines

Other biogenic monoamines

Polyamines

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Examples of notable biogenic polyamines include:

Physiological importance

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There is a distinction between endogenous and exogenous biogenic amines. Endogenous amines are produced in many different tissues (for example: adrenaline in adrenal medulla or histamine in mast cells and liver). Serotonin, an endogenous amine, is a neurotransmitter derived from the amino acid tryptophan. Serotonin is involved in regulating mood, sleep, appetite, and sexuality.[9] The amines are transmitted locally or via the blood system. The exogenous amines are directly absorbed from food in the intestine. Alcohol can increase the absorption rate. Monoamine oxidase (MAO) breaks down biogenic amines and prevents excessive resorption. MAO inhibitors (MAOIs) are also used as medications for the treatment of depression to prevent MAO from breaking down amines important for positive mood.

Importance in food

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Biogenic amines can be found in all foods containing proteins or free amino acids and are found in a wide range of food products including fish products, meat products, dairy products, wine, beer, vegetables, fruits, nuts and chocolate. In non-fermented foods the presence of biogenic amines is mostly undesired and can be used as indication for microbial spoilage. In fermented foods, one can expect the presence of many kinds of microorganisms, some of them being capable of producing biogenic amines. Some lactic acid bacteria isolated from commercial bottled yoghurt have been shown to produce biogenic amines. They play an important role as source of nitrogen and precursor for the synthesis of hormones, alkaloids, nucleic acids, proteins, amines and food aroma components. However, food containing high amounts of biogenic amines may have toxicological effects.[1]

Determination of biogenic amines in wines

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Biogenic amines are naturally present in grapes or can occur during the vinification and aging processes, essentially due to the microorganism's activity. When present in wines in high amount, biogenic amines may cause not only organoleptic defects but also adverse effects in sensitive human individuals, namely due to the toxicity of histamine, tyramine and putrescine. Even though there are no legal limits for the concentration of biogenic amines in wines, some European countries only recommend maximum limits for histamine. In this sense, biogenic amines in wines have been widely studied. The determination of amines in wines is commonly achieved by liquid chromatography, using derivatization reagents in order to promote its separation and detection. In alternative, other promising methodologies have been developed using capillary electrophoresis or biosensors, revealing lower costs and faster results, without needing a derivatization step. It is still a challenge to develop faster and inexpensive techniques or methodologies to apply in the wine industry.[medical citation needed]

See also

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References

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[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Biogenic amine

View on Grokipedia
from Grokipedia
Biogenic amines are low-molecular-weight organic compounds containing one or more groups, primarily synthesized through the enzymatic of or their derivatives in biological systems. These nitrogenous bases include key neurotransmitters such as the catecholamines—dopamine, , and epinephrine—derived from ; the indolamine serotonin from ; and from . Biogenic amines function as signaling molecules in the central and peripheral nervous systems, regulating processes like mood, , , sleep-wake cycles, and immune responses. In addition to their endogenous roles, biogenic amines are produced exogenously in fermented and spoiled foods via microbial of , where they serve as indicators of quality and can pose risks through or hypertensive crises in sensitive individuals. Classified structurally as aromatic (e.g., , phenylethylamine), aliphatic (e.g., , ), or heterocyclic (e.g., , serotonin), they are metabolized by enzymes like (MAO) and (DAO) to prevent accumulation. Dysregulation of biogenic amine levels is implicated in neurological disorders such as , depression, and , as well as gastrointestinal pathologies like . Their study spans biochemistry, , and , highlighting their dual significance in and .

Definition and Properties

Chemical Definition

Biogenic amines are low molecular weight organic nitrogen compounds formed primarily through the of or by and of aldehydes and ketones in metabolic processes of living organisms. These compounds are ubiquitous in , animals, microorganisms, and humans, distinguishing them from synthetic amines, which are produced through non-biological rather than enzymatic reactions in biological systems. Primary biogenic amines, the most common subclass, generally follow the structural formula \ceR−CH2−NH2\ce{R-CH2-NH2}, where RR is an alkyl or derived from the of the precursor . This structure arises directly from the of , which removes the carboxyl group (\ce−COOH\ce{-COOH}) while preserving the group and the carbon chain. For instance, undergoes to form , to , and to , each retaining the characteristic primary functionality from their origins.

Physical and Chemical Properties

Biogenic amines are generally highly -soluble due to their polar groups and often multiple sites, which facilitate their transport and in aqueous biological environments. For instance, exhibits a water solubility of approximately 535 mg/L experimentally, while norepinephrine is notably more soluble at 849 mg/L. This profile supports their roles in physiological processes, such as , by enabling rapid distribution across cellular compartments. Regarding volatility, biogenic amines possess moderate vapor pressures at room temperature, with boiling points typically ranging from 158°C for to 260°C for , allowing limited volatilization that aids in their detection and diffusion in gaseous or semi-aqueous systems like indicators. Unlike highly volatile amines such as (boiling point 2.8°C), biogenic amines are less prone to rapid but can still contribute to off-odors in biological and matrices through subtle vapor release. These compounds exhibit basicity characteristic of aliphatic or aromatic , with pKa values for the conjugate of the group typically falling between 8.8 and 10.2, rendering them protonatable in physiological ranges and reactive toward to form stable salts. Representative examples include (pKa 9.27 and 10.01), serotonin (pKa 9.31 and 10.0), and norepinephrine (pKa 8.85 and 9.5), which underscore their ability to exist as cations under mildly conditions, influencing their and interactions with biological receptors. In terms of reactivity, biogenic amines readily undergo oxidation, particularly those with catechol moieties like and norepinephrine, which can convert to quinones, aldehydes, or carboxylic acids via enzymatic or non-enzymatic pathways under neutral or alkaline conditions. They also form salts with acids and can participate in Maillard reactions during , where they react with reducing sugars under heat to produce melanoidins and flavor compounds. Additionally, in the presence of nitrites, biogenic amines such as and can form carcinogenic nitrosamines, a accelerated in acidic environments like cured meats. Stability of biogenic amines is notably sensitive to environmental factors, including , , and , leading to degradation that compromises their integrity in samples or products. Exposure to induces , particularly for catecholic amines, while elevated temperatures promote oxidative breakdown; acidification to below 3 with HCl enhances stability, allowing storage at room temperature for up to three days or at -80°C for months. At neutral or basic , they are prone to auto-oxidation, yielding products like nitrosamines under nitrosating conditions, which poses risks in contexts.
Biogenic AmineWater Solubility (mg/L, experimental)pKa Values (amine group)Boiling Point (°C)
Dopamine5359.27, 10.01~270 (decomposes)
Norepinephrine8498.85, 9.5225 (decomposes)
Serotonin25,5009.31, 10.0225 (decomposes)
PutrescineHighly soluble9.3, 10.7158
HistamineHighly soluble5.8, 9.8260 (decomposes)

Biosynthesis and Metabolism

Biosynthetic Pathways

Biogenic amines are primarily synthesized through the of precursor , a catalyzed by specific amino acid decarboxylase enzymes that remove the carboxyl group to yield the corresponding . This mechanism is conserved across various organisms, including mammals, microorganisms, and , and serves as the foundational biosynthetic route for both monoamines and polyamines. In mammals, (EC 4.1.1.22), a pyridoxal 5'-phosphate (PLP)-dependent enzyme, converts L-histidine to , playing a key role in immune and physiological responses. (AADC, EC 4.1.1.28), also PLP-dependent, primarily catalyzes the conversion of L-3,4-dihydroxyphenylalanine (), derived from L-tyrosine via , to , and 5-hydroxytryptophan (5-HTP), derived from L-tryptophan via , to serotonin. AADC can also decarboxylate L-tyrosine to and L-tryptophan to , producing trace levels of these biogenic amines. These PLP-requiring enzymes ensure efficient amine production, with regulation often tied to substrate availability and enzyme expression levels. Microbial biosynthesis contributes significantly to biogenic amine accumulation, particularly in fermented foods, where bacteria such as (e.g., and species) express decarboxylases during processes like cheese and wine production. For instance, tyrosine decarboxylase (EC 4.1.1.25) in these microbes transforms into , while generates from , often under anaerobic conditions that favor enzyme activity. The PLP cofactor is essential for these bacterial decarboxylases, enhancing their catalytic efficiency in nutrient-rich environments. In , decarboxylation pathways similarly rely on PLP-dependent enzymes to produce biogenic amines involved in growth and stress responses. decarboxylase (ADC, EC 4.1.1.19) and (ODC, EC 4.1.1.17) initiate synthesis by converting to and to , respectively, with subsequent steps yielding diamines like . Monoamine production, such as from , occurs via plant-specific tyrosine decarboxylases, contributing to in tissues like fruits and leaves. These pathways are upregulated during environmental stresses, underscoring their regulatory role via cofactor availability.

Degradation Mechanisms

Biogenic amines are primarily degraded through enzymatic processes that prevent their accumulation and mitigate potential in biological systems. The main degradation pathways involve oxidative and conjugation reactions, which convert these amines into less active metabolites for subsequent excretion. These mechanisms are crucial for maintaining , particularly in the , , and during . Oxidative deamination is a key catabolic route catalyzed by flavin-containing enzymes such as (MAO) and (DAO). MAO, located on the outer mitochondrial membrane, preferentially acts on monoamines like serotonin, , and norepinephrine, oxidizing them to corresponding aldehydes, which are further metabolized to carboxylic acids by , producing , , and as byproducts. There are two isoforms: MAO-A, which primarily degrades serotonin and norepinephrine, and MAO-B, which targets phenylethylamine and . DAO, a copper-containing , specifically degrades diamines and , converting histamine to imidazoleacetaldehyde via oxidative , followed by oxidation to imidazoleacetic acid. This process is prominent in the intestinal mucosa and kidneys, where DAO helps detoxify dietary histamine. In addition to oxidation, biogenic amines undergo conjugation reactions, such as or , to facilitate their inactivation and elimination. N-methyltransferase (HNMT), an intracellular abundant in the and other tissues, methylates at the ring to form N-methylhistamine, which is then oxidized by MAO to N-methylimidazoleacetic acid for renal excretion. This pathway predominates in the and complements DAO activity in peripheral tissues. Acetylation occurs less commonly but is observed in certain polyamines like , where it aids solubility for urinary clearance. Overall, conjugated metabolites are primarily eliminated via the kidneys, ensuring efficient removal from circulation. Microbial degradation plays a significant role in the gut and fermented foods, where such as Lactobacillus plantarum express amine oxidases and dehydrogenases that break down biogenic amines. These bacteria oxidize amines like , , and , reducing their levels through enzymatic conversion to aldehydes and subsequent non-toxic products. In the gut , diverse species contribute to this process, helping to mitigate amine accumulation from diet or endogenous production. Disruptions in these degradation pathways, such as through deficiencies or pharmacological inhibition, can lead to clinical implications. inhibitors (MAOIs), used in treating depression and , block MAO activity to elevate biogenic amine levels, enhancing but requiring dietary restrictions to avoid hypertensive crises from buildup. DAO deficiency, often genetic or acquired, is associated with , characterized by symptoms like headaches and gastrointestinal distress due to impaired breakdown. Low DAO activity serves as a for this condition, with studies confirming reduced levels in affected individuals.

Classification

Monoamines

Monoamines represent a primary subclass of biogenic amines, distinguished by possessing a single and typically synthesized through the of precursor by enzymes such as (AADC). These compounds are broadly categorized into structural subtypes, including catecholamines (derived from ), indolamines (derived from ), and imidazoles (derived from ), with additional trace amines forming a minor but distinct group. Prominent examples of monoamines include , formed by decarboxylation of the ; serotonin (5-hydroxytryptamine, or 5-HT), derived from ; and , produced from . Norepinephrine and epinephrine, both catecholamines, are sequentially synthesized from through and steps, respectively. These monoamines play essential roles in various physiological processes, though their detailed functions are addressed elsewhere. Trace amines constitute a structural subtype of monoamines, encompassing compounds like β-phenylethylamine (phenethylamine), , , and , which are generated from precursors such as and share structural similarities with classical monoamines but occur at lower concentrations. These trace amines can influence the activity of major monoaminergic systems, acting as neuromodulators in neural circuits. Monoamines exhibit widespread occurrence across multiple tissues, with high concentrations in where they serve as neurotransmitters in both central and peripheral systems. They are also abundant in the , particularly serotonin (over 90% of the body's total) produced by enterochromaffin cells and histamine by mucosal cells. In immune cells, such as mast cells, , and lymphocytes, monoamines like , serotonin, and are synthesized and released to modulate inflammatory responses and immune signaling.

Polyamines

Polyamines represent a subclass of biogenic amines distinguished by the presence of two or more groups within their molecular structure. These low-molecular-weight, aliphatic polycations are primarily synthesized through pathways involving the and . In most organisms, serves as the precursor for the diamine via the action of , while can yield through arginine decarboxylase, which may further convert to in certain species. Key examples of polyamines include (1,4-diaminobutane), a simple diamine directly derived from ; (1,5-diaminopentane), derived from , , a triamine formed by the addition of an aminopropyl group to putrescine; and , a tetramine resulting from a similar extension of spermidine. , another notable polyamine, arises specifically from and features a guanidino group alongside amine functionalities. These compounds exhibit structural diversity but share a common biosynthetic origin tied to . Structurally, polyamines consist of linear carbon chains interspersed with primary and secondary amine groups, enabling them to exist as polycations at physiological pH due to protonation of the nitrogen atoms. This charged configuration facilitates interactions with negatively charged biomolecules such as DNA and RNA. The positive charge and flexibility of these chains are conserved features across polyamine variants, contributing to their biological versatility. Polyamines are ubiquitous in prokaryotes, eukaryotes, and even , reflecting their fundamental role in cellular life. They occur at particularly high concentrations in rapidly proliferating cells, including embryonic tissues, tumor cells, and spermatozoa, where levels can exceed those in quiescent cells by several fold. This distribution underscores their association with dynamic cellular processes across diverse organisms.

Physiological Roles

Neurotransmission and Signaling

Biogenic amines, particularly monoamines, function as key neurotransmitters in the central and peripheral nervous systems, facilitating communication between neurons through synaptic transmission. , synthesized from , plays a central role in the , where it modulates motor control and reward processing via projections from the . , derived from and primarily originating from the , regulates mood, sleep-wake cycles, and emotional processing by influencing widespread cortical and limbic circuits. , produced from in noradrenergic neurons of the , enhances , , and stress responses through diffuse projections to the and . Histamine, formed from in tuberomammillary neurons of the , acts as a neuromodulator promoting and cognitive functions in the , while in the periphery it mediates allergic responses and . Its effects are transduced via four G-protein-coupled receptors (GPCRs): H1 and H2, which couple to and Gs proteins respectively to activate and pathways leading to IP3 and cAMP production; H3, which inhibits via Gi/o for presynaptic autoregulation; and H4, primarily expressed in immune cells but also influencing peripheral signaling. Similarly, monoamine signaling occurs predominantly through GPCRs, such as D1-like (Gs/cAMP) and D2-like (Gi/IP3) , 5-HT1/5-HT5/5-HT7 (Gi/cAMP) and 5-HT2/5-HT4/5-HT6 (Gq/IP3) serotonin receptors, and α/β-adrenergic receptors for norepinephrine, enabling diverse intracellular cascades that alter neuronal excitability and gene expression. Termination of these signals involves by specific transporters, including the (DAT) for , (SERT) for serotonin, and (NET) for norepinephrine, which recycle the amines into presynaptic terminals. Imbalances in biogenic amine underlie several neurological and psychiatric disorders. In , progressive loss of neurons in the results in striatal depletion, leading to motor symptoms like bradykinesia and rigidity. The serotonin hypothesis of depression posits reduced serotonergic activity in key circuits, contributing to mood dysregulation, though recent evidence suggests a more complex multifactorial etiology. is associated with hyperactivity in mesolimbic pathways, particularly excess signaling via D2 receptors in the , driving positive symptoms such as hallucinations. Dysregulated signaling, via H1 receptors, exacerbates allergic conditions and may contribute to sleep-wake disturbances in neuropsychiatric states.

Cellular Growth and Regulation

Biogenic amines, particularly polyamines such as putrescine, spermidine, and spermine, play crucial roles in cellular growth and regulation by interacting with nucleic acids and modulating key intracellular processes. These polycationic molecules bind to DNA and RNA through electrostatic interactions, stabilizing their structures and facilitating essential functions like replication and transcription. This binding condenses chromatin and protects nucleic acids from damage, thereby supporting cellular proliferation and differentiation. For instance, polyamines influence nucleosome assembly and gene expression by altering chromatin accessibility, which is vital for maintaining genomic integrity during rapid cell division. In the , spermidine and are integral to regulating protein via the hypusination of 5A (eIF5A), a process that enhances translational efficiency during growth phases such as . Hypusination, which incorporates a spermidine-derived moiety into eIF5A, promotes the synthesis of proteins necessary for and is dysregulated in conditions of aberrant growth. This mechanism links directly to progression, where depletion of these amines arrests cells in , underscoring their necessity for orderly division and . Polyamines also modulate and , with exhibiting anti-apoptotic effects by inhibiting activation and promoting cell survival pathways. Dysregulation of polyamine levels contributes to cancer progression, as tumors often display elevated concentrations of spermidine and , which sustain uncontrolled proliferation and evade . For example, in colorectal and cancers, heightened synthesis supports tumor growth by enhancing autophagy flux and resisting apoptotic signals. Beyond mammalian systems, polyamines contribute to cellular regulation in and microbes. In , they enhance stress responses, including in crops like and , by stabilizing membranes, scavenging , and upregulating stress-related genes. Exogenous application of spermidine or improves survival under water deficit by maintaining and root growth. In microbes, polyamines are essential for formation, promoting adhesion and matrix production in bacteria such as and , which facilitates community structure and environmental resilience.

Applications and Detection

Role in Food and Beverages

Biogenic amines form in fermented foods primarily through microbial of by such as and enterobacteria. In , accumulates via the conversion of , particularly in aged varieties like cheddar, where levels can reach significant concentrations due to prolonged microbial activity. Similarly, during wine , is produced from by malolactic , with red wines often exhibiting higher amounts owing to extended contact with grape skins and malolactic conversion processes. also generates biogenic amines like and through the action of fermenting microorganisms on , contributing to the product's characteristic profile during production. These compounds pose health risks when present in elevated concentrations, exerting vasoactive effects that may induce headaches, , or allergic-like reactions. A prominent example is scombroid poisoning, resulting from buildup in spoiled such as or , where rapid post-harvest leads to acute symptoms upon consumption. To address these concerns, the regulates levels in fishery products from species associated with high content, requiring an average not exceeding 100 mg/kg and no individual sample above 200 mg/kg, with limits up to 400 mg/kg for certain enzyme-ripened or fermented fishery products such as , based on sampling plans to ensure public safety. At low levels, biogenic amines can offer beneficial contributions to , notably enhancing flavor profiles; for instance, in , certain biogenic amines contribute to the complex sensory characteristics without adverse effects at controlled concentrations. The accumulation of these amines is modulated by environmental factors, including , where higher pH values (lower acidity) generally favor production, while more acidic conditions (lower ) inhibit it, and , as warmer conditions (20–37°C) accelerate microbial . Employing starter cultures devoid of decarboxylase enzymes, such as specific strains of Lactococcus lactis or Oenococcus oeni, effectively controls levels during , promoting safer and higher-quality products.

Analytical Determination Methods

The analytical determination of biogenic amines in biological samples, such as tissues, and food matrices, like wine and , relies on a combination of chromatographic, electrophoretic, and immunological techniques to achieve sensitive and selective quantification. These methods address the challenges posed by the polar, basic nature of biogenic amines, often requiring derivatization or preconcentration to enhance detectability and separate them from complex interferents. (HPLC) coupled with detection is a widely adopted approach, particularly using post-column or pre-column derivatization with o-phthaldialdehyde (OPA) to form highly fluorescent isoindoles. This technique enables the simultaneous analysis of multiple amines, such as , , and , with limits of detection typically in the range of 0.1–1 ng/mL after optimization. Gas chromatography-mass spectrometry (GC-MS) is particularly suited for volatile biogenic amines, like and , following derivatization to improve volatility and thermal stability. In food samples, such as , GC-MS provides structural confirmation via mass spectra, achieving quantification limits around 0.5–5 μg/g, and is valuable for profiling decomposition-related amines without extensive matrix interference. Sample preparation is crucial for these chromatographic methods, with (SPE) using mixed-mode cation-exchange/reversed-phase cartridges (e.g., Oasis MCX) commonly employed to isolate biogenic amines from complex matrices like wine or animal tissues. SPE minimizes co-extractives, such as proteins and phenolics, yielding recoveries of 85–105% for target amines and enabling cleaner injections for downstream analysis. Spectroscopic methods offer complementary separation and detection capabilities; (CE) excels in high-resolution separations of underivatized or derivatized biogenic amines based on charge-to-mass ratios in an . CE with UV or detection has been applied to biological fluids and , providing rapid analysis (under 10 minutes) with limits of detection as low as 0.5 μM for and . For rapid screening, enzyme-linked immunosorbent assay () is favored for in , utilizing specific antibodies to detect levels above regulatory thresholds (e.g., 50 mg/kg) with minimal and results in under 30 minutes. kits achieve sensitivities of 0.5–10 ng/mL, correlating well (r > 0.95) with chromatographic references for spoilage assessment. Recent advances include liquid chromatography-tandem (LC-MS/MS), which allows multi-amine profiling without derivatization using hydrophilic interaction columns, attaining limits of detection below 1 ng/mL for , , and in food extracts. This method's high specificity via multiple reaction monitoring reduces false positives in complex samples like or meat. Biosensors incorporating amine oxidases (e.g., or ) enable real-time monitoring by detecting produced during amine oxidation, often integrated with electrochemical transducers for portable applications in . These oxidase-based biosensors offer response times under 1 minute and detection limits of 0.1–1 μM, facilitating on-site quantification in beverages or tissues.

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