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Putrescine
Putrescine
Putrescine
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Putrescine
Skeletal formula of putrescine
Skeletal formula of putrescine
Ball and stick model of putrescine
Ball and stick model of putrescine
Names
Preferred IUPAC name
Butane-1,4-diamine
Other names
1,4-Diaminobutane, 1,4-Butanediamine
Identifiers
3D model (JSmol)
605282
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.003.440 Edit this at Wikidata
EC Number
  • 203-782-3
1715
KEGG
MeSH Putrescine
RTECS number
  • EJ6800000
UNII
UN number 2928
  • InChI=1S/C4H12N2/c5-3-1-2-4-6/h1-6H2 checkY
    Key: KIDHWZJUCRJVML-UHFFFAOYSA-N checkY
  • NCCCCN
Properties
C4H12N2
Molar mass 88.154 g·mol−1
Appearance Colourless crystals
Odor very unpleasant; putrid, fishy-ammoniacal
Density 0.877 g/mL
Melting point 27.5 °C (81.5 °F; 300.6 K)
Boiling point 158.6 °C; 317.4 °F; 431.7 K
Miscible
log P −0.466
Vapor pressure 2.33 mm Hg at 25 deg C (est)
3.54x10−10 atm-cu m/mol at 25 deg C (est)
1.457
Hazards
GHS labelling:
GHS02: Flammable GHS05: Corrosive GHS06: Toxic
Danger
H228, H302, H312, H314, H331
P210, P261, P280, P305+P351+P338, P310
Flash point 51 °C (124 °F; 324 K)
Explosive limits 0.98–9.08%
Lethal dose or concentration (LD, LC):
  • 463 mg kg−1 (oral, rat)
  • 1.576 g kg−1 (dermal, rabbit)
Related compounds
Related alkanamines
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine.[3] Together with cadaverine, it is largely responsible for the foul odor of putrefying flesh, but also contributes to other unpleasant odors.

Production

[edit]

Putrescine is produced on an industrial scale by the hydrogenation of succinonitrile.[3]

Biotechnological production of putrescine from a renewable feedstock has been investigated. A metabolically engineered strain of Escherichia coli that produces putrescine at high concentrations in glucose mineral salts medium has been described.[4]

Biochemistry

[edit]
Biosynthesis of spermidine and spermine from putrescine. Ado = 5'-adenosyl.

Spermidine synthase uses putrescine and S-adenosylmethioninamine (decarboxylated S-adenosyl methionine) to produce spermidine. Spermidine in turn is combined with another S-adenosylmethioninamine and gets converted to spermine.

Putrescine is synthesized in small quantities by healthy living cells by the action of ornithine decarboxylase.

Putrescine is synthesized biologically via two different pathways, both starting from arginine.

Putrescine, via metabolic intermediates including N-acetylputrescine, γ-aminobutyraldehyde (GABAL), N-acetyl-γ-aminobutyric acid (N-acetyl-GABAL), and N-acetyl-γ-aminobutyric acid (N-acetyl-GABA), biotransformations mediated by diamine oxidase (DAO), monoamine oxidase B (MAO-B), aminobutyraldehyde dehydrogenase (ABALDH), and other enzymes, can act as a minor biological precursor of γ-aminobutyric acid (GABA) in the brain and elsewhere.[6][7][8][9][10][11] In 2021, it was discovered that MAO-B does not mediate dopamine catabolism in the rodent striatum but instead participates in striatal GABA synthesis and that synthesized GABA in turn inhibits dopaminergic neurons in this brain area.[12][11] It has been found that MAO-B, via the putrescine pathway, importantly mediates GABA synthesis in astrocytes in various brain areas, including in the hippocampus, cerebellum, striatum, cerebral cortex, and substantia nigra pars compacta (SNpc).[12][11]

Occurrence

[edit]

Putrescine is found in all organisms.[13] Putrescine is widely found in plant tissues,[13] often being the most common polyamine present within the organism. Its role in development is well documented, but recent studies have suggested that putrescine also plays a role in stress responses in plants, both to biotic and abiotic stressors.[14] The absence of putrescine in plants is associated with an increase in both parasite and fungal population in plants.

Putrescine serves an important role in a multitude of ways, which include: a cation substitute, an osmolyte, or a transport protein.[13] It also serves as an important regulator in a variety of surface proteins, both on the cell surface and on organelles, such as the mitochondria and chloroplasts. A recorded increase of ATP production has been found in mitochondria and ATP synthesis by chloroplasts with an increase in mitochondrial and chloroplastic putrescine, but putrescine has also been shown to function as a developmental inhibitor in some plants, which can be seen as dwarfism and late flowering in Arabidopsis plants.[13]

Putrescine production in plants can also be promoted by fungi in the soil.[15] Piriformospora indica (P. indica) is one such fungus, found to promote putrescine production in Arabidopsis and common garden tomato plants. In a 2022 study it was shown that the presence of this fungus had a promotional effect on the growth of the root structure of plants. After gas chromatography testing, putrescine was found in higher amounts in these root structures.[16]

Plants that had been inoculated with P. indica had presented an excess of arginine decarboxylase.[16] This is used in the process of making putrescine in plant cells. One of the downstream effects of putrescine in root cells is the production of auxin. That same study found that putrescine added as a fertilizer showed the same results as if it was inoculated with the fungus, which was also shown in Arabidopsis and barley. The evolutionary foundations of this connection and putrescine are still unclear.

Putrescine is a component of bad breath and bacterial vaginosis.[17] It is also found in semen and some microalgae, together with spermine and spermidine.

Uses

[edit]

Putrescine reacts with adipic acid to yield the polyamide nylon 46, which is marketed by Envalior (formerly DSM) under the trade name Stanyl.[18][19]

Application of putrescine, along with other polyamines, can be used to extend the shelf life of fruits by delaying the ripening process.[20] Pre-harvest application of putrescine has been shown to increase plant resistance to high temperatures and drought.[21] Both of these effects seem to result from lowered ethylene production following exogenous putrescine exposure.[22]

Due to its role in putrification, putrescine has also been proposed as a biochemical marker for determining how long a corpse has been decomposing.[23]

Putrescine together with chitosan has been successfully used in postharvest physiology as a natural fruit coating.[24] Putrescine with chitosan treated fruits had higher antioxidant capacity and enzyme activities than untreated fruits. Fresh strawberries coated have lower decay percentage, higher tissue firmness, contents of total soluble solids. Nanoparticles of putrescine with chitosan are effective in preserving the nutritional quality and prolonging the post-harvest life of strawberries during storage up to 12 days.[24]

History

[edit]

Putrescine and cadaverine were first described in 1885 by the Berlin physician Ludwig Brieger (1849–1919).[25][26][27]

Toxicity

[edit]

In rats, putrescine has a low acute oral toxicity of 2000 mg/kg body weight, with no-observed-adverse-effect level of 2000 ppm (180 mg/kg body weight/day).[28]

Further reading

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Putrescine

View on Grokipedia
from Grokipedia
Putrescine, chemically known as butane-1,4-diamine, is an organic compound with the molecular formula C₄H₁₂N₂ and a key biogenic polyamine essential to cellular processes across all living organisms. As the foundational member of the polyamine family, putrescine is primarily synthesized through the decarboxylation of the amino acids ornithine or arginine via specific enzymes such as ornithine decarboxylase. It functions as a direct precursor to more complex polyamines like spermidine and spermine, which are critical for DNA stabilization, protein synthesis, and regulation of gene expression. In plants, putrescine plays a pivotal role in development, stress tolerance, and the biosynthesis of alkaloids such as nicotine through pathways involving putrescine N-methyltransferase. Beyond its biosynthetic importance, putrescine contributes to cellular fitness by acting as an , modulating ion balance, and influencing signaling pathways during growth and responses. In vertebrates, fungi, and , it is produced de novo and has been implicated in immune regulation, including the activation of . Additionally, putrescine accumulates in decaying animal tissues and spoiled foods due to bacterial activity, where it serves as a biochemical marker of and imparts a characteristic foul associated with . Emerging research highlights putrescine's therapeutic potential, including neuroprotective effects against aging and cognitive decline, as well as roles in mitigating and in various disease models. Its levels are tightly regulated, with dysregulation linked to pathological conditions such as cancer and neurodegenerative disorders.

Properties

Structure and nomenclature

Putrescine has the molecular formula C4H12N2C_4H_{12}N_2 and the H2N(CH2)4NH2H_2N(CH_2)_4NH_2, consisting of a four-carbon straight-chain with primary groups attached to the terminal carbons, also described as 1,4-butanediamine. The IUPAC name for putrescine is butane-1,4-diamine. The common name "putrescine" originates from its formation during , the bacterial decomposition of , deriving from the Latin "putrescere," meaning to rot or decay. Putrescine is classified as an aliphatic biogenic , produced naturally through of in biological systems. It serves as a key precursor in the of higher polyamines, such as spermidine.

Physical properties

Putrescine, a with the formula H₂N(CH₂)₄NH₂, is a colorless to slightly yellow, low-melting solid ( 27 °C) that becomes a above this . It has a melting point of 27 °C and a boiling point of 158–160 °C at . The density of liquid putrescine is 0.877 g/cm³ at 25 °C. Its molecular weight is 88.15 g/mol. Putrescine exhibits a foul, putrid associated with the scent of decaying . It is highly soluble in (approximately 1000 g/L at 20 °C) and soluble in alcohols and ethers.

Chemical properties

Putrescine, or 1,4-diaminobutane, exhibits basic properties characteristic of a , with the two primary amine groups conferring weak dibasic behavior. The pKa values for its conjugate acids are 9.35 and 10.8 (at 25 °C), reflecting the stepwise of the dicationic form in . These values indicate that putrescine predominantly exists as the dication at physiological , facilitating its interactions in biological and chemical systems. In terms of reactivity, putrescine readily forms salts with acids due to its basic nature; for instance, it reacts with to produce putrescine dihydrochloride, a stable crystalline salt commonly used in laboratory applications. Additionally, it undergoes polycondensation reactions with dicarboxylic acids, such as , to form polyamides like nylon-4,6, highlighting its utility as a in polymer synthesis. Putrescine demonstrates moderate stability under standard conditions but is hygroscopic, readily absorbing moisture from the air, which can affect its handling and storage. It is susceptible to oxidation by atmospheric oxygen, potentially leading to degradation products, though it remains stable in neutral aqueous solutions where such reactivity is minimized. Key reactions of putrescine include its role as a precursor in hydrogenation processes for industrial production, where succinonitrile is reduced to yield putrescine, and its ability to chelate metal ions through the lone pairs on its nitrogen atoms, forming complexes that can influence metal bioavailability in chemical and biological contexts.

Production

Biosynthesis

Putrescine is primarily synthesized in living organisms through the of L-ornithine, catalyzed by the (ODC). This rate-limiting step in converts L-ornithine into putrescine and , as represented by the reaction: L-ornithine→putrescine+CO2\text{L-ornithine} \rightarrow \text{putrescine} + \text{CO}_2 ODC is a pyridoxal 5'-phosphate-dependent highly conserved across eukaryotes and some prokaryotes, essential for maintaining cellular levels during growth and stress responses. An alternative biosynthetic pathway for putrescine originates from L-arginine and involves multiple enzymatic steps. Arginine decarboxylase (ADC) first converts L-arginine to , which is then hydrolyzed by agmatine iminohydrolase to N-carbamoylputrescine; subsequent hydrolysis by N-carbamoylputrescine amidohydrolase yields putrescine. This ADC-dependent route predominates in certain , , and under specific physiological conditions where ODC activity is limited, such as in the family. The activity of ODC is tightly regulated by intracellular concentrations through feedback inhibition, primarily mediated by the ODC antizyme, which binds ODC and targets it for ubiquitin-independent proteasomal degradation. Elevated levels of putrescine, spermidine, or induce antizyme synthesis via a unique +1 ribosomal frameshifting mechanism, thereby suppressing further ODC activity and preventing polyamine overaccumulation. Additionally, expression of the ODC gene is upregulated in response to growth-promoting signals, such as hormones or nutrients, through transcriptional activation involving factors like c-Myc in mammals. Putrescine produced via these pathways serves as a direct precursor for higher s like spermidine.

Industrial production

The primary industrial production of putrescine occurs via catalytic of succinonitrile (NC-CH₂-CH₂-CN), synthesized from and , using as the catalyst under high pressure and temperature conditions. This method delivers a high-purity product, typically achieving 99% purity or greater, which is essential for downstream applications in manufacturing. Alternative chemical routes include the reduction of derivatives and electroreduction of succinonitrile, though these are less prevalent in large-scale operations due to efficiency and cost considerations. Biotechnological advances have introduced sustainable alternatives, such as engineered strains overexpressing (ODC) for fermentative production from glucose as the carbon source. In high cell-density cultures, these strains have achieved titers of 24.2 g/L putrescine. More recent engineering efforts have reported titers up to 30 g/L from L-arginine as of 2024. Such methods leverage renewable feedstocks and aim to reduce reliance on precursors, with ongoing optimizations targeting higher yields for potential industrial scalability.

Biological role

Metabolic pathways

Putrescine serves as a central intermediate in metabolism, primarily undergoing conversion to higher polyamines through aminopropyl transfer reactions. The spermidine synthase (SRM or SPDS) catalyzes the transfer of an aminopropyl group from decarboxylated S-adenosylmethionine (dcSAM) to putrescine, yielding spermidine and 5'-methylthioadenosine (MTA) as a byproduct. This reaction is highly specific, with spermidine synthase exhibiting a strong preference for putrescine as the acceptor substrate. Spermidine, in turn, is further elongated by spermine synthase (SMS or SPMS), which adds another aminopropyl group from dcSAM to produce and MTA. These sequential steps maintain and support cellular processes requiring higher-order polyamines. Catabolism of putrescine occurs primarily through oxidative , mediated by copper-containing oxidases (CuAOs) or oxidases (PAOs). CuAOs oxidize one of putrescine's primary groups, generating 4-aminobutanal, (NH₃), and (H₂O₂). PAOs can also contribute, particularly in back-conversion pathways from higher s, producing similar aldehydic products and . The 4-aminobutanal intermediate is unstable and often cyclizes to Δ¹-pyrroline before further . The oxidative links turnover to signaling via H₂O₂ generation, with further of 4-aminobutanal to γ-aminobutyric acid () and then to succinic semialdehyde. Putrescine metabolism intersects with the (GABA) shunt in both and mammals, where catabolic products feed into GABA production. In , CuAO-mediated oxidation of putrescine yields 4-aminobutanal, which is converted to GABA by aminoaldehyde dehydrogenase (AMADH), bypassing parts of the tricarboxylic acid (TCA) cycle and enhancing stress resilience. This interconnection reprograms metabolism under low-temperature or abiotic stresses, with catabolism directly supplying precursors for the GABA shunt to mitigate . In mammals, similar oxidative pathways connect putrescine degradation to GABA synthesis, particularly in neural tissues, supporting homeostasis and integrating with TCA cycle flux during physiological demands.

Physiological functions

Putrescine plays a crucial role in cell growth and proliferation by stabilizing DNA and RNA structures, which is essential for processes such as mitosis and cell division. In rapidly dividing cells, including those in regenerative tissues, putrescine levels are elevated to support the transition through the G1 phase of the cell cycle and facilitate nucleic acid synthesis. Depletion of putrescine disrupts these functions, leading to inhibited proliferation, underscoring its necessity for maintaining cellular integrity during growth. In stress responses, putrescine accumulates in both and animals under conditions such as osmotic, oxidative, and wounding stress, acting as a compatible solute to stabilize proteins and scavenge (ROS). In , this accumulation enhances tolerance to and by modulating activity and reducing cellular damage, as seen in transgenic overexpressing decarboxylase. In animals, elevated putrescine levels in the following acute stress provide by counteracting oxidative damage and neuronal injury. Putrescine contributes to through its role in GABA synthesis, serving as a precursor via monoacetylputrescine degradation, which supports inhibitory signaling in glial cells and during . It also aids neuronal differentiation, with peak levels correlating to high activity during early development and proliferation. Regarding development, putrescine regulates embryogenesis and root growth in by promoting in meristems and interacting with signaling pathways, leading to enhanced root elongation in species like and . In mammals, it is implicated in , where peri-ovulatory supplementation reduces oocyte and improves quality in aged mice, supporting successful implantation and fetal growth. Putrescine also modulates immune responses, acting as a positive regulator of group 3 innate lymphoid cells (ILC3s) to promote production of cytokines such as IL-22 and IL-17, thereby supporting mucosal immunity and responses to . For , putrescine helps maintain balance by regulating synthesis through and preventing excessive , ensuring cellular viability under normal conditions. Imbalances in putrescine levels can disrupt this equilibrium, highlighting its role in sustaining overall across organisms.

Occurrence

In organisms

Putrescine is naturally present in various plant species, with levels varying during developmental stages. In Arabidopsis thaliana, putrescine concentrations in rosette leaves increase from vegetative to reproductive phases, reflecting changes in polyamine metabolism associated with growth transitions. Elevated putrescine levels are also observed in developing pollen, where it accumulates to support tube elongation, and in ripening fruits such as bananas, where free putrescine rises significantly in both pulp and peel tissues during climacteric maturation. In animals, putrescine occurs at elevated concentrations in reproductive fluids and certain tissues. Mammalian contains putrescine at levels approximately 0.3 mM, contributing to the overall profile alongside higher amounts of and spermidine. In human tissues, putrescine is detectable in the liver at higher concentrations in fetal stages compared to adults—up to threefold greater—and persists in adult regions, with regional variations influencing . Microorganisms produce putrescine as part of their metabolic responses, particularly under environmental pressures. In the bacterium , intracellular putrescine reaches up to 32 mM, with production and upregulated during nutrient stresses such as limitation to maintain cellular balance. In yeast, such as during processes, putrescine levels accumulate in the , increasing steadily as declines and correlating with turnover. Quantification of putrescine in biological samples typically employs (HPLC) coupled with (ESI-MS/MS), enabling sensitive detection of free putrescine alongside related polyamines like and spermidine in extracts from , animals, and microbes. Putrescine levels exhibit natural variations across species and conditions. In , putrescine displays diurnal fluctuations, with peaks often aligned to light-dark cycles and circadian rhythms, as seen in cold-responsive metabolites in Arabidopsis. In animal tissues, such as human liver, putrescine concentrations increase with age, showing significant elevation in older individuals compared to younger ones.

In decomposition

Putrescine forms during the of through bacterial of the , primarily by enzymes such as produced by like and species. This process occurs in protein-rich tissues after , where microbial activity breaks down cellular components, releasing putrescine alongside from , both contributing to the characteristic foul of decay often described as putrid or rotten. In advanced stages of , such as autolysis and , these biogenic amines accumulate rapidly, peaking within hours to days depending on environmental factors like and oxygen levels. In food spoilage, putrescine serves as a key indicator of microbial degradation in products like , cheese, and wine, where elevated concentrations signal bacterial activity and reduced quality. For instance, in fresh , a Biogenic Amine Index (putrescine + + + ) below 5 mg/kg suggests good condition, while concentrations exceeding 50 mg/kg denote spoilage due to by contaminants such as . In aged cheeses and fermented sausages, tolerable thresholds reach up to 360 mg/kg, beyond which the amine imparts off-flavors and health risks from microbial overgrowth. Similarly, in wine, putrescine levels typically range from 2 to 20 mg/L in quality products, but surges above 100 mg/L during improper or storage indicate spoilage by . Forensic applications leverage putrescine's accumulation in postmortem tissues to estimate the (PMI), as its levels in brain cortex and other organs rise predictably with time since . Studies using gas chromatography-mass spectrometry have shown putrescine concentrations correlating with PMI up to 48 hours, offering higher accuracy than alone due to its faster production rate by decomposing . This aids in narrowing timelines when combined with activity and observations. Environmentally, putrescine appears as a in and , arising from the breakdown of organic waste by anaerobic bacteria. In systems, it contributes to malodors and can reach concentrations of several mg/L in untreated effluents, while in composting processes, it transiently accumulates during the thermophilic phase before degrading. Its presence in these matrices reflects microbial cycling but diminishes with proper aeration and control. High putrescine levels also manifest in certain health-related decomposition-like processes, such as halitosis () from oral bacterial breakdown of proteins, producing detectable amounts via Porphyromonas and Fusobacterium species. In bacterial vaginosis, vaginal fluid exhibits significantly elevated putrescine (alongside and ) compared to healthy states, correlating with dominated by Gardnerella vaginalis and contributing to the associated fishy odor.

Applications

Industrial uses

Putrescine serves as a key in the production of nylon-4,6, a high-performance commercialized by DSM under the trade name Stanyl, through polycondensation with . This polymer exhibits superior mechanical properties, including high heat resistance, wear resistance, and dimensional stability compared to traditional like nylon-6,6, making it suitable for demanding applications in automotive components such as engine covers, gears, and electrical connectors, as well as in for housings and insulators. The synthesis leverages putrescine's structure to form strong amide bonds, enabling the material's use in environments requiring long-term durability under thermal and mechanical stress. As a chemical intermediate, putrescine is utilized in the synthesis of various pharmaceuticals and agrochemicals, where its groups facilitate derivatization into complex molecules. In pharmaceutical production, it acts as a building block for compounds targeting metabolic pathways, while in agrochemicals, it contributes to the development of and active ingredients that enhance efficacy and compatibility. These applications highlight putrescine's versatility as a platform chemical, though its role remains niche due to the compound's specific reactivity. Global production of putrescine is estimated in the range of several hundred tons annually, primarily driven by demand from the sector, with market values projected to reach approximately USD 400-700 million by the early 2030s. Recent advancements post-2020 have focused on bio-based routes, including microbial of engineered Escherichia coli and Corynebacterium glutamicum strains to produce putrescine from renewable feedstocks like glucose, enabling sustainable nylon-4,6 synthesis with reduced reliance on petrochemical-derived sources. These developments, such as the integration of transcriptional biosensors for high-throughput strain optimization, have achieved titers up to 76 g/L in lab-scale fermentations, paving the way for scalable bio-nylon production.

Agricultural and therapeutic uses

In agriculture, putrescine is applied as a foliar spray to enhance tolerance to abiotic stresses such as and heat. For instance, exogenous application of putrescine at concentrations of 1-2 mM has been shown to alleviate terminal stress in plants by improving antioxidant enzyme activities and maintaining , thereby increasing yield under water-limited conditions. Similarly, combined foliar sprays of putrescine (1 mM) with have enhanced productivity in drought-prone areas by reducing oxidative damage and promoting growth during the reproductive phase. These applications leverage putrescine's natural role in plant stress responses, where it modulates to stabilize cell membranes and scavenge . Dosage levels typically range from 1-5 mM for effective foliar treatments, balancing efficacy with minimal . Putrescine also extends the postharvest shelf life of fruits by inhibiting ethylene biosynthesis, a key regulator of ripening. Preharvest or postharvest treatments with putrescine (1-2 mM) on plum, mango, and tomato fruits have reduced respiration rates, ethylene production, and softening enzyme activities, thereby delaying senescence and preserving firmness for up to 30 days longer than untreated controls. In blueberries, putrescine application at 2 mM maintained fruit quality attributes like color and weight loss, extending marketable shelf life through suppressed ethylene-mediated ripening. In therapeutic contexts, putrescine-related interventions target cancer via inhibition of (ODC), the enzyme catalyzing its synthesis, to disrupt -dependent tumor growth. ODC inhibitors such as α-difluoromethylornithine (DFMO) and methylacetylenic putrescine analogs deplete intracellular putrescine levels, inducing antiproliferative effects in various malignancies; for example, phase I trials of methylacetylenic putrescine demonstrated safety and reduction in advanced cancer patients. Combined ODC inhibition with transport blockers has shown synergistic tumor suppression in preclinical models by limiting putrescine availability for cancer cell proliferation. Putrescine promotes in animal models by enhancing and tissue repair processes. In weanling piglet models of intestinal , dietary putrescine supplementation (0.2% w/w) mitigated mucosal damage by suppressing and improving epithelial integrity post-weaning. Similarly, putrescine treatment in piglet models activated matrix metalloproteinase-9 (MMP9)-mediated via signaling, accelerating vascularization and recovery. In , putrescine serves as a supplement in media to promote mammalian and productivity. Addition of 10-25 μM putrescine to ovary () s enhanced proliferation, yields, and metabolic efficiency by activating signaling pathways. It also functions as a component in vectors, where putrescine-conjugated polycations facilitate DNA into cancer cells; for example, putrescine-based nanotherapies reduced tumor growth in mouse models by enabling targeted with low . Recent research from 2023-2025 highlights putrescine's potential in control and . Bacterial-derived algicides containing high putrescine concentrations (up to 1 mM) have inhibited harmful s in marine mesocosms by disrupting growth without non-target effects on ecosystems. In neurodegeneration models, modulation including putrescine supplementation alleviated α-synuclein aggregation in models by regulating interconversion enzymes, improving motor function and neuronal survival. These findings underscore putrescine's emerging role in addressing environmental and neurological challenges through targeted applications.

History

Discovery

Putrescine was first isolated in 1885 by German physician Ludwig Brieger from putrefied animal tissue during his investigations into ptomaines, a class of toxic amines produced by bacterial decomposition of proteins. Brieger's work focused on identifying these substances as potential causes of food poisoning and decay-related illnesses, extracting the compound from decomposed pancreatic tissue of animals. Brieger coined the name "putrescine" for the compound, derived from the Latin word putresco, meaning "to become rotten" or "to decay," highlighting its association with the of rotting . Early characterization revealed it as a due to its strong basicity, which allowed it to form salts with acids, though its exact was determined in subsequent years through further analysis. This discovery occurred alongside that of , another isolated from similar putrefactive processes.

Scientific developments

In the mid-20th century, putrescine was identified as a crucial precursor in during the late 1950s by Herbert Tabor and Celia White Tabor, in collaboration with Sanford M. Rosenthal, who described its quantification and metabolic pathways in bacterial and mammalian systems. Their work established putrescine as the foundational from which higher s like spermidine and are derived, marking a pivotal shift from its prior recognition merely as a product to a vital cellular component. During the 1960s, the enzyme (ODC) was discovered and characterized as the rate-limiting catalyst converting to putrescine, with early purifications from rat and bacterial sources highlighting its inducible nature in response to growth stimuli. This breakthrough enabled detailed studies on regulation, revealing ODC's rapid turnover and sensitivity to feedback inhibition by putrescine itself. The biochemical era of the 1970s and 1980s focused on elucidating the full biosynthetic and catabolic pathways, including the roles of S-adenosylmethionine decarboxylase in transferring aminopropyl groups to putrescine for spermidine formation. Concurrently, linked putrescine dysregulation to cancer, as ODC overexpression was observed in rapidly proliferating tumor cells, elevating putrescine levels and promoting ; seminal studies by Russell and Snyder in the laid the groundwork, with 1970s-1980s experiments confirming ODC as a therapeutic target via inhibitors like α-difluoromethylornithine (DFMO). Entering the 2000s, advancements in enabled biotechnological production of putrescine, with engineered strains achieving high yields from renewable feedstocks like glucose, reaching up to 1.68 g/L in early reports and scaling to over 20 g/L by optimized pathways in Corynebacterium glutamicum. These developments provided sustainable alternatives to , emphasizing putrescine's industrial potential while deepening insights into pathway flux control. From the 2010s to 2025, research has illuminated putrescine's role in stress signaling across organisms, particularly in where exogenous application mitigates abiotic stresses like and by modulating and , as shown in and models. In animals, putrescine contributes to cellular resilience under via homeostasis. Interactions with have gained prominence, with microbial consortia collectively biosynthesizing putrescine from or , influencing host physiology. Recent metabolomics applications have positioned putrescine as a in profiling, such as in and cancer metabolomes, using techniques like LC-MS to track pathway perturbations for diagnostic and therapeutic insights. Key milestones include indirect connections to Nobel-recognized work on S-adenosylmethionine (SAM), discovered by Giulio Cantoni in 1951 as the methyl donor and aminopropyl precursor essential for putrescine-derived synthesis, underpinning decades of biochemical advancements.

Toxicity

Acute effects

Putrescine exhibits low acute oral toxicity, with an LD50 of approximately 2000 mg/kg body weight in rats, indicating a relatively low risk from single ingestions but potential for gastrointestinal irritation such as at high doses. In subacute studies, oral administration at 2000 ppm led to decreased feed intake, body weight gain, and dose-dependent gastrointestinal effects in rats. Upon inhalation or dermal contact, putrescine acts as a strong irritant to the eyes, , and mucous membranes, potentially causing severe burns, redness, and respiratory distress at elevated concentrations. Its foul , characteristic of , is detectable at very low levels, with thresholds reported around 100 ppm, serving as an early warning for exposure. Acute symptoms from high-dose exposure include , , and , often exacerbated in cases of intoxication from spoiled food, where putrescine contributes to scombroid-like by potentiating effects. This intoxication manifests as flushing, , and allergic-like reactions due to impaired breakdown. The primary mechanism involves putrescine-induced release from mast cells and inhibition of , which normally metabolizes both compounds, though rapid enzymatic degradation by and limits the severity of acute effects. No specific OSHA permissible exposure limit (PEL) has been established for putrescine, but it is handled and stored as a corrosive irritant requiring protective equipment to prevent acute exposure.

Long-term exposure

Prolonged exposure to putrescine, a biogenic , poses chronic health risks primarily through its role in formation and disruption of physiological . In environments with presence, such as processed meats or acidic conditions, putrescine reacts to amplify the production of N-nitrosodimethylamine (NDMA), a potent linked to long-term oncogenic potential. High dietary intake of putrescine from amine-rich foods exacerbates gastric mucosal damage and increases the risk of gastrointestinal disorders, as biogenic amines potentiate and impair digestive function over time. Additionally, chronic accumulation of putrescine as a uremic toxin contributes to renal impairment, , and cardiovascular complications by altering cellular balance. In occupational settings, repeated of putrescine vapors or dust leads to respiratory and potential , resulting in airways disease characterized by persistent difficulties. Workers handling putrescine in industrial or environments face heightened risks of chronic respiratory issues due to cumulative exposure, with long-term effects including and reduced function. Furthermore, dysregulation of metabolism, including putrescine bioaccumulation, underlies disorders such as , where elevated levels promote nucleolar disruption and neuronal damage over extended periods. Environmentally, putrescine contributes to toxicity in polluted aquatic systems by interacting with algal communities, as demonstrated in recent studies on dinoflagellates. In nitrogen-enriched waters, putrescine synergizes with to disrupt , reducing algal tolerance and altering microbial carbon and cycling, which elevates total carbon and levels in sediments and promotes broader ecological imbalances. These interactions, observed in riverine and marine contexts, amplify in contaminated habitats, affecting and . Epidemiologically, elevated putrescine levels are associated with increased risk and progression of certain cancers, notably , where polyamine dysregulation serves as a of . Studies indicate higher urinary and tissue concentrations of putrescine in patients, correlating with tumor aggressiveness and poor prognosis due to its role in . The compound's essentiality in normal cellular function creates a narrow therapeutic window, where chronic excess from dietary or endogenous sources heightens oncogenic potential without clear safe thresholds for prolonged exposure. Mitigation strategies for long-term putrescine exposure emphasize dietary regulation and . Establishing tolerable levels—such as maximums of 140–510 mg/kg in foods like , fish, and fermented products—helps limit chronic dietary accumulation and associated gastric risks. In occupational contexts, maintaining well-ventilated areas, using respiratory protection, and adhering to exposure limits prevent respiratory and .

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Putrescine
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC8293435/
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC9491463/
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC8955586/
  5. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/putrescine
  6. https://pubmed.ncbi.nlm.nih.gov/32017122/
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC10520894/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC5783396/
  9. https://www.sciencedirect.com/science/article/abs/pii/S0014299924004928
  10. https://biosignaling.biomedcentral.com/articles/10.1186/s12964-023-01373-0
  11. https://www.aging-us.com/article/100361/text
  12. https://go.drugbank.com/drugs/DB01917
  13. https://scijournals.onlinelibrary.wiley.com/doi/10.1002/jsfa.10928
  14. https://www.sciencedirect.com/topics/[neuroscience](/page/Neuroscience)/putrescine
  15. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8210315.htm
  16. https://www.sigmaaldrich.com/US/en/product/sial/51799
  17. https://pmc.ncbi.nlm.nih.gov/articles/PMC4551835/
  18. https://sitem.herts.ac.uk/aeru/bpdb/Reports/1393.htm
  19. https://pubchem.ncbi.nlm.nih.gov/compound/Putrescine-Dihydrochloride
  20. https://www.uniprot.org/uniprotkb/P00860/entry
  21. https://www.sciencedirect.com/science/article/pii/S0021925820723926
  22. https://pubmed.ncbi.nlm.nih.gov/24648395/
  23. https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2019.00320/full
  24. https://amb-express.springeropen.com/articles/10.1186/s13568-021-01330-5
  25. https://pubmed.ncbi.nlm.nih.gov/11123206/
  26. https://www.embopress.org/doi/10.1038/sj.emboj.7600473
  27. https://www.jbc.org/article/S0021-9258%2820%2972392-6/pdf
  28. https://academic.oup.com/jxb/article/56/414/1105/551487
  29. https://www.sciencedirect.com/science/article/abs/pii/S1369703X20304137
  30. https://www.chemicalbook.com/article/putrescine-and-cadaverine.htm
  31. https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/bit.22502
  32. https://pubmed.ncbi.nlm.nih.gov/39260727/
  33. https://phys.org/news/2009-08-industrially-vital-chemical-bacteria.html
  34. https://www.uniprot.org/uniprotkb/P19623/entry
  35. https://doi.org/10.3390/medsci10030038
  36. https://www.uniprot.org/uniprotkb/P52788/entry
  37. https://doi.org/10.1038/s41568-018-0050-3
  38. https://onlinelibrary.wiley.com/doi/10.1111/tpj.17094
  39. https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2022.1035414/full
  40. https://phmd.hirszfeld.pl/wp-content/uploads/2023/07/1098147.pdf
  41. https://pmc.ncbi.nlm.nih.gov/articles/PMC3823250/
  42. https://www.sciencedirect.com/topics/neuroscience/putrescine
  43. https://pmc.ncbi.nlm.nih.gov/articles/PMC6439130/
  44. https://pmc.ncbi.nlm.nih.gov/articles/PMC6741638/
  45. https://academic.oup.com/jxb/article/65/5/1285/2884855
  46. https://pubmed.ncbi.nlm.nih.gov/17097300/
  47. https://www.sciencedirect.com/science/article/abs/pii/S0031942297002112
  48. https://www.nature.com/articles/s41598-024-70137-8
  49. https://www.mdpi.com/1422-0067/22/1/441
  50. https://www.nature.com/articles/pr1974128.pdf
  51. https://pubmed.ncbi.nlm.nih.gov/7616219/
  52. https://onlinelibrary.wiley.com/doi/10.1155/2024/7120208
  53. https://onlinelibrary.wiley.com/doi/abs/10.1002/j.2050-0416.1983.tb04198.x
  54. https://pubmed.ncbi.nlm.nih.gov/26340761/
  55. https://pubmed.ncbi.nlm.nih.gov/21124901/
  56. https://pubmed.ncbi.nlm.nih.gov/32995657/
  57. https://onlinelibrary.wiley.com/doi/abs/10.1111/1541-4337.12099
  58. https://pmc.ncbi.nlm.nih.gov/articles/PMC10538644/
  59. https://www.mdpi.com/2304-8158/8/2/62
  60. https://www.ages.at/en/human/nutrition-food/residues-contaminants-from-a-to-z/biogenic-amines
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC9783241/
  62. https://www.sciencedirect.com/science/article/abs/pii/S0379073819300283
  63. https://ejfsat.journals.ekb.eg/article_156221_16047d8d4ddc2f262894f7048b00e3a2.pdf
  64. https://www.pjoes.com/pdf-62096-23798?filename=Determining%2520Eight.pdf
  65. https://compostfoundation.org/i/
  66. https://www.ncbi.nlm.nih.gov/books/NBK534859/
  67. https://pmc.ncbi.nlm.nih.gov/articles/PMC4586437/
  68. https://pubs.acs.org/doi/10.1021/acssuschemeng.3c05247
  69. https://onlinelibrary.wiley.com/doi/pdf/10.1002/bit.22502
  70. https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-016-0411-0
  71. https://pubs.acs.org/doi/abs/10.1021/acssuschemeng.9b05484
  72. https://www.sciencedirect.com/science/article/abs/pii/S0960852424011751
  73. https://pubmed.ncbi.nlm.nih.gov/24706212/
  74. https://www.verifiedmarketresearch.com/product/putrescine-market/
  75. https://pubmed.ncbi.nlm.nih.gov/36829651/
  76. https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2022.1000877/full
  77. https://pse.agriculturejournals.cz/artkey/pse-202401-0004_sole-and-combined-foliar-application-of-silicon-and-putrescine-alleviates-the-negative-effects-of-drought-stres.php
  78. https://www.nature.com/articles/s41598-025-11180-x
  79. https://www.tandfonline.com/doi/full/10.1080/15538362.2022.2068733
  80. https://www.mdpi.com/2223-7747/11/10/1356
  81. https://pubmed.ncbi.nlm.nih.gov/2713957/
  82. https://www.sciencedirect.com/science/article/pii/S0304383521003050
  83. https://jasbsci.biomedcentral.com/articles/10.1186/s40104-019-0379-9
  84. https://www.sciencedirect.com/science/article/pii/S0891584923012030?via%253Dihub
  85. https://pubmed.ncbi.nlm.nih.gov/36947192/
  86. https://pubs.rsc.org/en/content/articlehtml/2023/bm/d2bm01456d
  87. https://www.researchgate.net/publication/397093849_Controlling_harmful_algal_blooms_HABs_in_marine_waters_Review_of_current_status_and_future_prospects
  88. https://www.nature.com/articles/s41531-025-01087-9
  89. https://victorianweb.org/science/biology/bacteriology/brieger.html
  90. https://pubmed.ncbi.nlm.nih.gov/31762052/
  91. https://www.sciencedirect.com/science/article/pii/S0308814623021763
  92. https://www.tandfonline.com/doi/full/10.4161/psb.25850
  93. https://www.sciencedirect.com/science/article/pii/S0021925820311753
  94. https://pubmed.ncbi.nlm.nih.gov/20219382/
  95. https://pmc.ncbi.nlm.nih.gov/articles/PMC4027058/
  96. https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2021.767992/full
  97. https://pmc.ncbi.nlm.nih.gov/articles/PMC6397830/
  98. https://www.tandfonline.com/doi/full/10.1080/1354750X.2021.1875506
  99. https://pubmed.ncbi.nlm.nih.gov/4299947/
  100. https://www.researchgate.net/publication/7593616_An_Escape_from_Italy_the_Discovery_of_S-Adenosylmethionine_and_the_Biosynthesis_of_Creatine_by_Giulio_L_Cantoni
  101. https://pubmed.ncbi.nlm.nih.gov/9207896/
  102. https://www.researchgate.net/publication/230055110_Apparent_odor_thresholds_of_polyamines_in_water_and_2_soybean_flour_dispersions
  103. https://pubmed.ncbi.nlm.nih.gov/19234946/
  104. https://pmc.ncbi.nlm.nih.gov/articles/PMC7305651/
  105. https://link.springer.com/article/10.1007/BF01993133
  106. https://pubmed.ncbi.nlm.nih.gov/25213924/
  107. https://www.researchgate.net/publication/228083797_Dietary_exposure_assessment_of_putrescine_and_cadaverine_and_derivation_of_tolerable_levels_in_selected_foods_consumed_in_Austria
  108. https://store.apolloscientific.co.uk/storage/msds/BIB6265_msds.pdf
  109. https://www.carlroth.com/downloads/sdb/en/4/SDB_4141_GB_EN.pdf
  110. https://journals.sagepub.com/doi/10.3233/JAD-231184
  111. https://pmc.ncbi.nlm.nih.gov/articles/PMC10816187/
  112. https://www.sciencedirect.com/science/article/abs/pii/S0013935122023969
  113. https://www.mdpi.com/2218-273X/12/4/514
  114. https://pubmed.ncbi.nlm.nih.gov/35964654/
  115. https://www.szabo-scandic.com/media/product_data/msds/SAC/SAC-MSDS-SACSC-202786.pdf
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