PRODUCTS

EICOSATETRAENOIC ACID

Eicosatetraenoic acid is utilized in cell culture experiments to modulate signaling pathways linked to growth, differentiation, and apoptosis.
Eicosatetraenoic Acid is employed in analytical chemistry as a reference compound for lipid profiling and fatty acid identification.
In medical research, eicosatetraenoic acid is studied for its potential role in cardiovascular health and inflammatory diseases.

CAS Number: 506-32-1
EC Number: 208-033-4
Molecular Formula: C20H32O2
Molecular Weight: 304.5 g/mol

SYNONYMS:
eicosatetraenoic acid, SCHEMBL25208, CHEBI:166893, arachidonic acid, (5Z,8Z,11Z,14Z)-5,8,11,14-icosatetraenoic acid, 5,8,11,14-eicosatetraenoic acid, icosa-5Z,8Z,11Z,14Z-tetraenoic acid, (all-Z)-5,8,11,14-eicosatetraenoic acid, All-cis-5,8,11,14-eicosatetraenoic acid, C20:4(ω-6), Arachidonate, 6,10,14,18-eicosatetraenoic acid, 799LCD4RYS, 6,10,14,18-Icosatetraenoic acid, 6,10,14,18-Icosatetraenoic-acid, 6,10,14,18-Eicosatetraenoic-acid, (6E,10E,14E,18E)-icosa-6,10,14,18-tetraenoic acid, 854251-31-3, 6, 10, 14, 18-icosatetraenoic acid, (6E,10E,14E,18E)-Icosa-6,10,14,18-tetraenoic-acid, C20:4n-2,6,10,14, RefChem:103685, UNII-799LCD4RYS, LMFA01030175, SCHEMBL466177, CHEBI:192884, (5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoic acid[1], 5,8,11,14-all-cis-Eicosatetraenoic acid, all-cis-5,8,11,14-Eicosatetraenoic acid

Eicosatetraenoic acid refers to a class of straight-chain, 20-carbon polyunsaturated fatty acids (PUFAs) containing four C=C double bonds somewhere along the hydrocarbon chain.
In formal IUPAC terms these are icosa-n, n+3, n+6, n+9-tetraenoic acids depending on exact double-bond position.

Eicosatetraenoic acid (ETA) designates any straight chain tetra-unsaturated 20-carbon fatty acid.
These compound are classified as polyunsaturated fatty acids (PUFA).
The pure compounds, which are encountered rarely, are colorless oils.

Two isomers, both of them as fatty acids, are of particular interest:
all-cis-5,8,11,14-eicosatetraenoic acid is an ω-6 fatty acid with the trivial name arachidonic acid.
It is formed by a desaturation of dihomo-gamma-linolenic acid (DGLA, 20:3 ω-6).
all-cis-8,11,14,17-eicosatetraenoic acid is an ω-3 fatty acid.

Eicosatetraenoic Acid is an intermediate between stearidonic acid (18:4 ω-3) and eicosapentaenoic acid (EPA, 20:5 ω-3).
Some chemistry sources define 'arachadonic acid' to designate any of the eicosatetraenoic acids.
However, almost all writings in biology, medicine, and nutrition limit the use of the term 'arachidonic acid' to all-cis-5,8,11,14-eicosatetraenoic acid (ω-6).

Eicosatetraenoic acid is an omega-3 fatty acid.
Eicosatetraenoic Acid is a polyunsaturated long-chain fatty acid with a 20-carbon backbone and exactly 4 double bonds.
Eight different isomers can be called by this name.

Eicosatetraenoic acid (ETA) refers to the family of polyunsaturated, long-chain fatty acids with a 20-carbon backbone and four double bonds.
There are eight total isomers of Eicosatetraenoic Acid.
Arachidonic acid, an omega-6 fatty acid, is the most prevalent and well-studied isomer.
Though uncommon, some Eicosatetraenoic Acids are essential fatty acids found in some fungi, fish oils, and human and animal fat tissue.

Other Eicosatetraenoic Acids, including arachidonic acid, can be synthesized by the elongation and dehydration of shorter essential fatty acids, including linoleic acid.
Eicosatetraenoic Acids directly impact a variety of physiological states, and their impact is largely effected by their derivatives, which are bioactive compounds including epoxide eicosatrienoic acids (EETs), lipoxins (LXs), and hydroxyeicosatetraenoic acids (HETEs).

Variants of each of these molecules are associated with cancers, cardiovascular diseases, inflammation, and other conditions; and further metabolization of these compounds leads to the production of prostaglandins, leukotrienes, and other immune signaling molecules.
Eicosatetraenoic acid belongs to a small but chemically important family of long-chain polyunsaturated fatty acids characterized by a twenty-carbon backbone and four cis double bonds.

The presence of multiple cis unsaturations introduces pronounced conformational flexibility into the hydrocarbon chain, resulting in a highly kinked structure that prevents tight molecular packing.
This structural feature explains Eicosatetraenoic Acid's low melting point and its strong ability to increase membrane fluidity when esterified into phospholipids.

From a stereochemical standpoint, naturally occurring eicosatetraenoic acids are almost exclusively found in the all-cis (Z) configuration.
Trans isomers are rare in nature and are typically generated only under harsh chemical processing conditions.
The cis geometry is critical for biological recognition by enzymes such as cyclooxygenases, lipoxygenases, and acyltransferases, which display high stereospecificity.

In biological systems, eicosatetraenoic acid is not primarily present as a free fatty acid.
Instead, Eicosatetraenoic Acid is esterified at the sn-2 position of glycerophospholipids, especially phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol.

Upon cellular stimulation—such as mechanical stress, immune activation, or hormonal signaling—phospholipase A₂ enzymes release free eicosatetraenoic acid, initiating downstream signaling cascades.
This release step is often rate-limiting and tightly regulated.

Metabolically, eicosatetraenoic acid occupies a central position in lipid signaling.
Eicosatetraenoic Acid serves as the direct precursor for multiple classes of bioactive mediators collectively known as eicosanoids.
These include prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipoxins, and various epoxy- and hydroxy-derivatives.

Each metabolite exhibits distinct physiological effects, influencing inflammation, platelet aggregation, vascular tone, bronchial reactivity, and immune cell chemotaxis.
The same parent molecule can therefore yield both pro-inflammatory and inflammation-resolving mediators depending on enzymatic context.

From an analytical chemistry perspective, eicosatetraenoic acid is commonly characterized using gas chromatography (GC) after derivatization to its methyl ester (FAME).
Due to Eicosatetraenoic Acid's high degree of unsaturation, careful control of temperature and oxygen exposure is required during analysis to prevent oxidative degradation.

High-performance liquid chromatography (HPLC), particularly reversed-phase and silver-ion chromatography, is also widely used to resolve positional and geometric isomers.
Structural confirmation is typically achieved by mass spectrometry and nuclear magnetic resonance spectroscopy, especially ¹H-NMR and ¹³C-NMR, which clearly reveal cis double-bond patterns.

Eicosatetraenoic Acid is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14).
Eicosatetraenoic Acid is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes.
Together with omega−3 fatty acids and other omega−6 fatty acids, Eicosatetraenoic Acid provides energy for body functions, contributes to cell membrane structure, and participates in the synthesis of eicosanoids, which have numerous roles in physiology as signaling molecules.

Eicosatetraenoic Acid was named after the similarly structured Arachidic acid, a constituent of peanut oil whose name in turn derives from the ancient Greek neologism arachis 'peanut'.
Peanut oil does not contain any arachidonic acid, itself.

Arachidonate is the name of the derived carboxylate anion (conjugate base of the acid), salts, and some esters.
Eicosatetraenoic acid (ETA) is a polyunsaturated fatty acid characterized by a 20-carbon chain and four double bonds, belonging to the class of long-chain unsaturated fatty acids essential for cellular structure and signaling.

Eicosatetraenoic Acid encompasses several isomers.
In biochemical contexts, Eicosatetraenoic Acid often specifically refers to the omega-3 isomer, while the omega-6 form is commonly known as arachidonic acid.

The most biologically significant include Eicosatetraenoic Acid (all-cis-5,8,11,14-eicosatetraenoic acid, 20:4 n-6), an omega-6 fatty acid derived from linoleic acid and stored in cell membrane phospholipids, and cis-8,11,14,17-eicosatetraenoic acid (20:4 n-3), a minor omega-3 fatty acid found in marine lipids.

These isomers play critical roles as precursors to eicosanoids, a family of signaling molecules that mediate inflammation, vascular tone, and immune responses through enzymatic pathways such as cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450.
Eicosatetraenoic Acid, in particular, is released from membranes by phospholipases upon cellular activation and is metabolized into pro-inflammatory prostaglandins, thromboxanes, and leukotrienes, influencing processes like platelet aggregation, fever, and pain sensation.

In contrast, the omega-3 isomer (20:4 n-3) is metabolized in human platelets primarily to 12-hydroxy-8,10,14,17-eicosatetraenoic acid and exhibits inhibitory effects on prostaglandin synthesis while activating 12-lipoxygenase, contributing to anti-thrombotic and cardioprotective actions observed in marine-derived n-3 polyunsaturated fatty acids.

Eicosatetraenoic Acids are obtained through dietary sources—arachidonic acid from animal fats and the omega-3 form from fish oils and algae—and their balance in the diet is linked to health outcomes, with omega-3 variants potentially counteracting the pro-inflammatory effects of omega-6 derivatives to reduce risks of cardiovascular disease and chronic inflammation.

Dysregulation of Eicosatetraenoic Acid metabolism, such as excessive arachidonic acid-derived eicosanoids, is implicated in pathologies including hypertension, atherosclerosis, and allergic responses, highlighting their dual roles in homeostasis and disease.
In terms of chemical stability, eicosatetraenoic acid is highly susceptible to autoxidation.

The bis-allylic methylene groups located between double bonds are particularly vulnerable to radical attack, leading to peroxide formation and secondary oxidation products such as aldehydes and ketones.
For this reason, Eicosatetraenoic Acid must be stored under inert atmosphere, protected from light, and often stabilized with antioxidants such as tocopherols.

This instability significantly influences Eicosatetraenoic Acid's shelf life and handling requirements in both laboratory and industrial environments.
Industrially, eicosatetraenoic acid is produced primarily through enzymatic or chemical hydrolysis of natural lipid sources, followed by purification.

Animal tissues and microbial fermentation products are common raw materials.
Highly purified grades are used in pharmaceutical research, while lower-purity material may be used in nutritional or biochemical applications.
Due to regulatory scrutiny, food and supplement uses are subject to strict purity, oxidation index, and contaminant limits.

From a regulatory and safety standpoint, eicosatetraenoic acid is generally regarded as a biologically active substance rather than a simple inert fatty acid.
Finally, from a functional chemistry perspective, eicosatetraenoic acid illustrates how molecular structure dictates biological behavior.

The combination of chain length, unsaturation degree, and stereochemistry makes Eicosatetraenoic Acid uniquely suited for rapid enzymatic conversion and signaling, distinguishing it sharply from saturated or monounsaturated fatty acids.
This dual identity—as both a structural membrane component and a dynamic signaling precursor—makes Eicosatetraenoic Acid one of the most intensively studied fatty acids in modern biochemistry and lipid science.

USES and APPLICATIONS of EICOSATETRAENOIC ACID:
Eicosatetraenoic acid is used in biochemical research as a precursor for studying the synthesis of eicosanoids involved in inflammation and cell signaling.
Eicosatetraenoic Acid is applied in lipid metabolism studies to understand the role of polyunsaturated fatty acids in membrane structure and function.

In pharmacological research, eicosatetraenoic acid is used to investigate pathways related to inflammatory mediators and immune responses.
Eicosatetraenoic Acid has applications in nutritional science for examining the biological effects of omega-3 and omega-6 fatty acid derivatives.

Eicosatetraenoic Acid is also used in experimental studies exploring the relationship between fatty acid composition and neurological function.
Biochemical research: Eicosatetraenoic Acid is used to study lipid signaling and inflammatory pathways.
Dietary supplements: Marketed (in limited context) as an essential fatty acid.

Food and nutrition science: Investigated in context of lipid metabolism and health.
Cosmetic formulations: Explored for skin-related metabolic effects.
These uses appear in chemical suppliers and product descriptions.

-Biological Role and Uses
Biological & Nutritional Role:
Eicosatetraenoic Acid is an important component of cell membranes, especially in brain, muscle, liver, and immune cells.

Eicosatetraenoic Acid is a precursor in the biosynthesis of eicosanoids (prostaglandins, thromboxanes, leukotrienes) — key signaling molecules in inflammation, immunity, and vascular tone.
As an omega-6 PUFA, Eicosatetraenoic Acid influences membrane fluidity and cellular signaling.

POTENTIAL HEALTH APPLICATIONS of EICOSATETRAENOIC ACID:
Eicosatetraenoic acid (ETA, 20:4 n-3) has been investigated for its potential role in managing inflammatory conditions, particularly as an adjunctive therapy in rheumatoid arthritis.
By inhibiting phospholipase A2 activity, Eicosatetraenoic Acid reduces the release of arachidonic acid and subsequent production of pro-inflammatory eicosanoids, offering anti-inflammatory benefits without generating potent inflammatory mediators.

This mechanism supports its use in suppressing joint inflammation and symptoms like pain and stiffness in rheumatoid arthritis models.
In cardiovascular disease, Eicosatetraenoic Acid demonstrates cardio-protective effects, attributed to its competition with arachidonic acid in cyclooxygenase-2 and lipoxygenase pathways, thereby modulating inflammatory responses that contribute to atherosclerosis.

Supplementation with Eicosatetraenoic Acid is particularly relevant for vegetarians and vegans, where algal or microbial sources provide a non-animal alternative to increase tissue levels of this omega-3 intermediate.
Strategies often involve combining Eicosatetraenoic Acid with DHA and EPA in formulated supplements to enhance overall n-3 PUFA bioavailability and eicosanoid balance.

Eicosatetraenoic Acid exhibits a favorable safety profile, generally recognized as safe (GRAS) by the FDA when incorporated into algal oils as a food additive, with no adverse effects observed in toxicological studies of DHA-rich oils containing trace Eicosatetraenoic Acid at levels below 0.0033 g/100 g.

Doses up to 3 g/day of combined n-3 PUFAs, including Eicosatetraenoic Acid precursors, are well-tolerated in adults, though caution is advised for interactions with anticoagulants due to potential mild blood-thinning effects from omega-3 fatty acids.
Emerging research highlights Eicosatetraenoic Acid's potential in cancer prevention through the production of anti-angiogenic eicosanoids derived from its metabolism, though human trials are needed.

Ongoing investigations explore Eicosatetraenoic Acid's role in neurodegenerative diseases, leveraging anti-inflammatory pathways to mitigate neuronal damage.
Eicosatetraenoic Acid holds GRAS status as a food additive but is not approved as a pharmaceutical drug.

RESEARCH AND APPLICATIONS of EICOSATETRAENOIC ACID:
Key Studies
Eicosatetraenoic acid (ETA, 20:4 n-3), an intermediate in the omega-3 polyunsaturated fatty acid biosynthetic pathway, was first identified in the mid-20th century as part of early research on lipid metabolism.

During the 1950s, studies on polyunsaturated fatty acids in marine sources highlighted Eicosatetraenoic Acid's presence alongside longer-chain omega-3s like eicosapentaenoic acid (EPA).

Seminal work in the 1960s and 1970s, including contributions from researchers like Donald Sprecher, elucidated the desaturation and elongation steps leading to Eicosatetraenoic Acid from alpha-linolenic acid, establishing its role in omega-3 pathways.
In the 1990s, research began exploring Eicosatetraenoic Acid's potential anti-inflammatory effects, building on broader omega-3 studies.

Trials demonstrated that omega-3 intermediates like Eicosatetraenoic Acid could modulate inflammatory responses by competing with arachidonic acid-derived eicosanoids, leading to reduced production of pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-alpha.
Cardiovascular research in the late 1990s incorporated Eicosatetraenoic Acid within the context of mixed omega-3 supplementation from fish oils.

The GISSI-Prevenzione trial, published in 1999, involved over 11,000 patients post-myocardial infarction and found that daily supplementation with 1 g of omega-3 ethyl esters (primarily EPA and DHA, with trace amounts of other n-3 fatty acids including Eicosatetraenoic Acid) reduced overall mortality by 10% and sudden cardiac death by 45%, attributing benefits to anti-arrhythmic and anti-thrombotic effects of n-3 fatty acids.

More recent investigations in the 2010s have focused on Eicosatetraenoic Acid from sustainable, vegan sources such as algal and plant-derived oils.
A 2016 phase I randomized clinical trial examined Ahiflower oil (from Buglossoides arvensis seeds, rich in stearidonic acid that converts to
Eicosatetraenoic Acid) in 40 healthy subjects, showing significant dose-dependent increases in plasma Eicosatetraenoic Acid levels compared to flaxseed oil, with safe tolerability and enhanced long-chain n-3 enrichment.

This built on earlier algal research, highlighting Eicosatetraenoic Acid's bioavailability for non-fish diets.
Post-2016 studies have further explored Eicosatetraenoic Acid's anti-inflammatory potential.
A 2021 review highlighted Eicosatetraenoic Acid's role in producing specialized pro-resolving mediators that aid in inflammation resolution, with emerging evidence from models suggesting benefits in chronic inflammatory diseases.

Despite these advances, key studies on Eicosatetraenoic Acid face limitations, including small sample sizes in human trials (often n<50) and a reliance on surrogate markers like plasma levels rather than hard clinical endpoints.
Larger, long-term randomized controlled trials are needed to confirm Eicosatetraenoic Acid's specific contributions beyond general omega-3 effects, as current evidence is predominantly from short-term or mechanistic studies.

PRECURSORS TO EICOSANOIDS:
Eicosanoids, a diverse family of signaling molecules, are produced by oxygenation of polyunsaturated eicosatetraenoic acids.
The eicosanoids, working in tandem, contribute to a lipid signaling complex widely responsible for inducing an inflammatory immune response.
Common signs of inflammation are both internal and external, with effects like visible redness, pain in the surrounding area, swelling, and the sensation of heat—many of these an effect of varying eicosanoid species.
These effects are associated with and have been observed in patients with cancers and various neurological/metabolic disorders.

RELATED STUDIES of EICOSATETRAENOIC ACID:
Eicosatetraenoic Acid is found in green-lipped mussel and appears to inhibit the oxygenation of arachidonic acid by both the cyclooxygenase (COX) and lipoxygenase pathways.
Mutant of Mortierella alpina 1S-4 is a fungus employed for producing arachidonic acid.
These mutants produce larger amounts of Eicosatetraenoic Acid due to the expression of an ω-3-desaturase gene, typically responsible for the significant production of the more abundant PUFAs.
In addition to their inflammatory nature, eicosanoids such as Eicosatetraenoic Acid can also contribute to an anti-inflammatory response.

METABOLIC TRANSFORMATIONS of EICOSATETRAENOIC ACID:
Eicosatetraenoic acid (ETA) isomers, derived from elongation of stearidonic acid (for 20:4 n-3) or dihomo-gamma-linolenic acid (for 20:4 n-6), undergo several key metabolic transformations in mammalian tissues.
Primarily, Eicosatetraenoic Acid is broken down via mitochondrial beta-oxidation, where it is sequentially oxidized to generate acetyl-CoA units, which enter the citric acid cycle to produce energy.

This process involves activation to Eicosatetraenoic Acid-CoA, followed by dehydrogenation, hydration, and thiolysis steps, similar to other polyunsaturated fatty acids (PUFAs).
Eicosatetraenoic Acid also serves as a substrate for oxidative enzymes, particularly in the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, leading to the formation of specialized eicosanoids.

In the omega-3 pathway, 20:4 n-3 is converted by COX-1 or COX-2 to prostaglandin endoperoxides, which can yield 3-series prostaglandins such as prostaglandin I3 (PGI3).
The LOX pathway, especially 5-LOX, metabolizes 20:4 n-3 to hydroxyeicosatetraenoic acids (HETEs) and leukotriene precursors, including novel metabolites like Δ17-8-hydroxy-eicosatetraenoic acid.

For the omega-6 isomer, arachidonic acid (20:4 n-6) is metabolized to 2-series prostaglandins (e.g., PGI2), thromboxanes, and 4-series leukotrienes, which are pro-inflammatory.
These transformations occur predominantly in inflammatory cells and vascular tissues.

For chain shortening and eventual excretion, peroxisomal beta-oxidation plays a role in processing Eicosatetraenoic Acid, particularly when incorporated into very long-chain derivatives or during retroconversion processes.
This pathway shortens the fatty acid chain by removing two-carbon units, producing shorter omega-3 PUFAs that can be further metabolized or eliminated via urine and bile.

Unlike mitochondrial oxidation, peroxisomal beta-oxidation generates hydrogen peroxide and is crucial for handling unsaturated chains like those in Eicosatetraenoic Acid.

Eicosatetraenoic Acid is distributed mainly in the liver, brain, and adipose tissue, where it accumulates in phospholipids and triacylglycerols, reflecting its roles in membrane fluidity and lipid storage.
Metabolic regulation of Eicosatetraenoic Acid is modulated by dietary intake of precursor omega-3 fatty acids, which upregulates its levels, and by inflammatory states that enhance COX and LOX activity through cytokine signaling.

BIOLOGICAL FUNCTIONS of EICOSATETRAENOIC ACID:
Role as Eicosanoid Precursor
Eicosatetraenoic acid (ETA), specifically the omega-3 isomer 20:4 n-3 (all-cis-8,11,14,17-eicosatetraenoic acid), functions as a biochemical precursor to various eicosanoids through enzymatic oxidation pathways.

Upon release from membrane phospholipids by phospholipase A2, Eicosatetraenoic Acid is metabolized primarily via cyclooxygenase (COX) and lipoxygenase (LOX) enzymes to generate less inflammatory mediators compared to those derived from arachidonic acid (20:4 n-6).
This role positions Eicosatetraenoic Acid as a key player in modulating inflammatory responses by competing with arachidonic acid for these enzymes.

In the COX pathway, Eicosatetraenoic Acid serves as a substrate for both COX-1 and COX-2 isoforms, which catalyze its conversion to the intermediate prostaglandin H3 (PGH3).
PGH3 is then transformed by downstream synthases into 3-series prostaglandins, such as prostaglandin I3 (PGI3) and prostaglandin D3 (PGD3), as well as thromboxane A3 (TXA3).

These 3-series eicosanoids exhibit reduced potency in promoting inflammation and platelet aggregation relative to their 2-series counterparts from arachidonic acid; for instance, TXA3 induces weaker vasoconstriction and thrombosis than TXA2.
This enzymatic processing occurs predominantly in endothelial cells, where prostacyclin synthase converts PGH3 to PGI3, contributing to vasodilation.

Via the 5-LOX pathway, Eicosatetraenoic Acid is oxygenated to 5-hydroperoxy-8,11,14,17-eicosatetraenoic acid (5-HPETE), which rearranges to leukotriene A5 (LTA5).
LTA5 is subsequently hydrolyzed by LTA4 hydrolase to leukotriene B5 (LTB5) or conjugated by LTC4 synthase to cysteinyl leukotrienes like LTC5, forming 5-series leukotrienes overall.

These metabolites demonstrate diminished chemotactic and pro-inflammatory activities compared to 4-series leukotrienes from arachidonic acid, such as LTB4, with LTB5 showing reduced neutrophil recruitment.

This metabolism is prominent in leukocytes, including neutrophils, monocytes, and macrophages, where 5-LOX is highly expressed and activated by cellular stimuli.
Novel Eicosatetraenoic Acid-derived 5-LOX products, like Δ17-8,15-diHETE, further exhibit anti-inflammatory effects by inhibiting LTB4-mediated chemotaxis.

DIETARY SOURCES of EICOSATETRAENOIC ACID:
Eicosatetraenoic acid (ETA, 20:4 n-3), a long-chain omega-3 polyunsaturated fatty acid, occurs in small amounts in various marine-derived foods, contributing modestly to human dietary intake.
Primary sources include fatty fish such as herring and sardines, where Eicosatetraenoic Acid typically comprises 0.4–0.7% of total fatty acids in the lipid profile.

For instance, in White Sea herring (Clupea pallasii marisalbi), Eicosatetraenoic Acid levels range from 0.42 ± 0.04% to 0.66 ± 0.03% of total fatty acids, depending on the sampling location, reflecting variations in environmental conditions.

Other seafood, notably New Zealand green-lipped mussel (Perna canaliculus), serves as a concentrated natural source of Eicosatetraenoic Acid, particularly in lipid extracts valued for anti-inflammatory properties.
Algae-derived oils from certain microalgae species also contain Eicosatetraenoic Acid, though often in trace quantities alongside more abundant EPA and DHA.

Plant-based sources of Eicosatetraenoic Acid are limited and generally provide only trace amounts.
Some marine macroalgae and seaweeds can be enriched with Eicosatetraenoic Acid through environmental factors or processing, offering minimal contributions to dietary intake.

Dietary supplements provide another avenue for Eicosatetraenoic Acid consumption, including fish oil capsules (containing approximately 1% ETA relative to total lipids), algal oil products, and green-lipped mussel extracts.
Typical servings of these supplements can contribute to daily Eicosatetraenoic Acid intake, with population studies reporting average dietary consumption around 0.16 g/day from food sources alone, excluding supplements.

There is no specific recommended dietary allowance (RDA) for Eicosatetraenoic Acid; however, general guidelines for omega-3 fatty acids suggest 250–500 mg/day of EPA and DHA (as part of total long-chain n-3 PUFAs) for adults to support cardiovascular health, into which Eicosatetraenoic Acid intake may indirectly fit.
Eicosatetraenoic Acid bioavailability is enhanced when consumed with meals containing dietary fats, similar to other lipid-soluble omega-3s.

BIOSYNTHESIS AND METABOLISM of EICOSATETRAENOIC ACID:
Biosynthetic Pathways
Eicosatetraenoic acid (ETA) refers to several isomers, with biosynthesis differing by omega series.
The omega-3 isomer (20:4ω-3) is synthesized through the aerobic desaturation-elongation pathway of polyunsaturated fatty acids, primarily from the essential precursor alpha-linolenic acid (ALA, 18:3ω-3), which must be obtained from the diet.

The pathway begins with the action of delta-6-desaturase (encoded by FADS2 homologs), which introduces a double bond at the Δ6 position of ALA to form stearidonic acid (SDA, 18:4ω-3).
This is followed by elongation via C18-to-C20 elongase enzymes (such as Elovl2/5-like), adding two carbons to produce Eicosatetraenoic Acid with double bonds at positions 8,11,14,17.

The parallel omega-6 pathway produces arachidonic acid (20:4ω-6, the most biologically significant Eicosatetraenoic Acid isomer) from linoleic acid (LA, 18:2ω-6).
Delta-6-desaturase converts LA to gamma-linolenic acid (GLA, 18:3ω-6), which is elongated to dihomo-gamma-linolenic acid (DGLA, 20:3ω-6), and then delta-5-desaturase (FADS1) forms arachidonic acid.

This biosynthetic route is highly efficient in certain organisms, particularly marine algae such as Nannochloropsis oceanica and Phaeodactylum tricornutum, where delta-6-desaturase and elongases show high activity in converting ALA to SDA and SDA to Eicosatetraenoic Acid, often enhanced under nutrient stress conditions like nitrogen limitation.

In fish, such as salmon, endogenous synthesis from ALA is limited, with most Eicosatetraenoic Acid accumulation occurring through dietary uptake from algal sources in the marine food chain, though some species exhibit moderate desaturase and elongase activity adapted to cold environments.

In contrast, human biosynthesis is inefficient, with overall conversion from ALA to longer-chain omega-3 fatty acids like Eicosatetraenoic Acid occurring at rates below 5-10%, due to low enzyme expression and competition from the parallel omega-6 pathway.
Genetic variations in the FADS1 and FADS2 gene cluster on chromosome 11 significantly modulate this efficiency in humans.

FADS2 variants, such as rs174537 (G allele), enhance delta-6-desaturase activity and thus ALA desaturation to SDA, while FADS1 polymorphisms influence downstream steps; carriers of efficiency-boosting alleles show 20-50% higher LC-PUFA levels, with effects varying by ancestry (e.g., higher in African populations).
These genetic factors underscore the reliance on dietary Eicosatetraenoic Acid precursors in individuals with low-activity variants.

ALTERNATIVE PARENTS of EICOSATETRAENOIC ACID:
*Unsaturated fatty acids
*Straight chain fatty acids
*Monocarboxylic acids and derivatives
*Carboxylic acids
*Organic oxides
*Hydrocarbon derivatives
*Carbonyl compounds

SUBSTITUENTS of EICOSATETRAENOIC ACID:
*Long-chain fatty acid
*Unsaturated fatty acid
*Straight chain fatty acid
*Monocarboxylic acid or derivatives
*Carboxylic acid
*Carboxylic acid derivative
*Organic oxygen compound
*Organic oxide
*Hydrocarbon derivative
*Organooxygen compound
*Carbonyl group
*Aliphatic acyclic compound

DIETARY SUPPLEMENT of EICOSATETRAENOIC ACID:
Eicosatetraenoic Acid is marketed as a dietary supplement.
A 2019 review of clinical studies investigating the potential health effects of Docosahexaenoic Acid supplementation of up to 1500 mg per day on human health found there were no clear benefits.

There were no adverse effects in adults of using high daily doses (1500 mg) of Docosahexaenoic Acid on several biomarkers of blood chemistry, immune function, and inflammation.

A 2009 review indicated that consumption of 5−10% of food energy from omega−6 fatty acids including Docosahexaenoic Acid may reduce the risk of cardiovascular diseases compared to lower intakes.

A 2014 meta-analysis of possible associations between heart disease risk and individual fatty acids reported a significantly reduced risk of heart disease with higher levels of EPA, DHA, and Docosahexaenoic Acid.

CHEMICAL PROPERTIES of EICOSATETRAENOIC ACID:
Structure and Nomenclature
Eicosatetraenoic acid (ETA) is a class of polyunsaturated fatty acids with a 20-carbon chain and four double bonds.
The omega-3 isomer, also known as 20:4ω-3 or 20:4(n-3), is characterized by a straight-chain hydrocarbon backbone of 20 carbon atoms with four cis double bonds and a carboxylic acid functional group.

Its molecular formula is C20H32O2.
The structure consists of a 20-carbon chain where the double bonds are located at positions Δ8, Δ11, Δ14, and Δ17 (counting from the carboxyl end), all in the cis (Z) configuration, making it an omega-3 fatty acid due to the position of the terminal double bond three carbons from the methyl end.

The carboxylic acid group is attached to carbon 1, enabling its role in lipid metabolism.
The systematic IUPAC name for this omega-3 isomer of Eicosatetraenoic Acid is (8Z,11Z,14Z,17Z)-icosa-8,11,14,17-tetraenoic acid, reflecting the positions and configurations of the double bonds.

It is commonly abbreviated as ETA, distinguishing it from other eicosatetraenoic acids, and denoted in shorthand notation as 20:4(n-3) or 20:4ω-3 to indicate the chain length, number of double bonds, and omega-3 positioning.

In comparison to the related omega-6 fatty acid arachidonic acid (20:4ω-6), Eicosatetraenoic Acid differs in the positioning of its double bonds: arachidonic acid has cis double bonds at Δ5, Δ8, Δ11, and Δ14, shifting the series toward the carboxyl end and altering its metabolic pathway.
This structural distinction influences their respective roles as precursors in eicosanoid synthesis.

PHYSICAL AND CHEMICAL CHARACTERISTICS of EICOSATETRAENOIC ACID:
Eicosatetraenoic acid is insoluble in water but readily soluble in organic solvents such as ethanol and chloroform.
Due to its polyunsaturated structure with four double bonds, eicosatetraenoic acid is highly susceptible to oxidation, potentially forming explosive peroxides upon exposure to air; storage typically requires antioxidants and inert atmospheres to maintain stability.
Eicosatetraenoic acid is optically inactive, as it lacks chiral centers.

OCCURRENCE AND SOURCES of EICOSATETRAENOIC ACID:
Natural Occurrence
Eicosatetraenoic acid (ETA, 20:4 n-3), an omega-3 polyunsaturated fatty acid, is primarily synthesized by marine microorganisms and serves as a key intermediate in the biosynthesis of longer-chain omega-3 fatty acids.
Eicosatetraenoic Acid occurs naturally in various marine algae and phytoplankton, though typically at low levels compared to other PUFAs like EPA (20:5 n-3).

These primary producers form the base of aquatic food webs, enabling Eicosatetraenoic Acid accumulation in higher trophic levels.
In animal tissues, Eicosatetraenoic Acid is present in the lipids of cold-water fish such as salmon (Salmo salar) and mackerel (Scomber scombrus), where it comprises trace amounts, typically less than 1% of total fatty acids in muscle and liver phospholipids.

This presence reflects dietary intake from algal sources, with levels varying based on fish diet and habitat; for example, wild salmon exhibit slightly higher proportions than farmed varieties due to natural foraging.
Minor amounts of Eicosatetraenoic Acid are also found in mammalian phospholipids, such as in human plasma, where it appears as a metabolic intermediate at trace levels (around 0.1%).

Eicosatetraenoic Acid accumulates in aquatic ecosystems through trophic transfer, starting from microalgae and phytoplankton consumed by zooplankton, which are then ingested by small fish and ultimately larger predatory species like salmon and mackerel.
This bioaccumulation process concentrates omega-3 fatty acids in marine food chains, contributing to the high PUFA content in cold-water environments.

TRADITIONAL AND SCIENTIFIC VALIDATION of EICOSATETRAENOIC ACID:
Eicosatetraenoic acid (ETA) is an omega-3 polyunsaturated fatty acid found in certain marine sources, such as fish oils and some algae.
Historically, the recognition of omega-3 fatty acids’ health benefits emerged from studies of populations with high seafood consumption, notably the Inuit, who exhibited lower rates of cardiovascular disease.

While EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) have been more extensively studied, interest in Eicosatetraenoic Acid has grown due to its unique role in human physiology.
Recent scientific investigations suggest that Eicosatetraenoic Acid may contribute to anti-inflammatory processes by modulating the production of eicosanoids, signaling molecules involved in the body’s inflammatory response.

Some preclinical studies indicate Eicosatetraenoic Acid can inhibit enzymes such as cyclooxygenase (COX) and lipoxygenase, potentially reducing the synthesis of pro-inflammatory mediators.
Early clinical research, although limited, has shown promising outcomes for Eicosatetraenoic Acid in supporting joint health and reducing markers of inflammation.

Furthermore, Eicosatetraenoic Acid may exert synergistic effects when combined with other omega-3 fatty acids, enhancing their overall efficacy in nutritional products.
Eicosatetraenoic Acid's inclusion in dietary supplements and functional foods is based on these potential benefits and its presence in natural food sources traditionally associated with positive health outcomes.

While more robust clinical trials are needed to fully establish Eicosatetraenoic Acid’s efficacy and mechanisms of action, current evidence supports its valuable contribution as part of a balanced intake of omega-3 fatty acids.
Ongoing research is expected to further elucidate its health-promoting properties.

CHEMICAL CHARACTERISTICS AND BEHAVIOR of EICOSATETRAENOIC ACID:
Reactivity:
Double bonds make ETA susceptible to oxidation and peroxidation, particularly in biological systems (leading to eicosanoid production).
Undergoes metabolism via cyclooxygenase (COX), lipoxygenase (LOX), and P450 enzyme pathways to yield signaling mediators.

Solubility & Stability:
Low water solubility, typical for long-chain fatty acids.
Sensitive to heat and oxygen — can degrade or polymerize if improperly stored.

BIOSYNTHESIS AND CASCADE IN HUMANS of EICOSATETRAENOIC ACID:
Eicosatetraenoic Acid is freed from phospholipids by hydrolysis, catalyzed by the phospholipase A2 (PLA2).
Eicosatetraenoic Acid for signaling purposes appears to be derived by the action of group IVA cytosolic phospholipase A2 (cPLA2, 85 kDa), whereas inflammatory arachidonic acid is generated by the action of a low-molecular-weight secretory PLA2 (sPLA2, 14-18 kDa).

Eicosatetraenoic Acid is a precursor to a wide range of eicosanoids:
The enzymes cyclooxygenase-1 and -2 (i.e. prostaglandin G/H synthase 1 and 2 [PTGS1 and PTGS2]) convert Eicosatetraenoic Acid to prostaglandin G2 and prostaglandin H2, which in turn may be converted to various prostaglandins, to prostacyclin, to thromboxanes, and to the 17-carbon product of thromboxane metabolism of prostaglandin G2/H2, 12-hydroxyheptadecatrienoic acid (12-HHT).

The enzyme 5-lipoxygenase catalyzes the oxidation of Eicosatetraenoic Acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which in turn converts to various leukotrienes (i.e., leukotriene B4, leukotriene C4, leukotriene D4, and leukotriene E4) as well as to 5-hydroxyeicosatetraenoic acid (5-HETE) which may then be further metabolized to 5-HETE's more potent 5-keto analog, 5-oxo-eicosatetraenoic acid (5-oxo-ETE).

The enzymes 15-lipoxygenase-1 (ALOX15) and 15-lipoxygenase-2 (ALOX15B).
ALOX15B catalyzes the oxidation of Eicosatetraenoic Acid to 15-hydroperoxyeicosatetraenoic acid (15-HPETE), which may then be further converted to 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins.

15-Lipoxygenase-1 may also further metabolize 15-HPETE to eoxins in a pathway analogous to (and presumably using the same enzymes as used in) the pathway which metabolizes 5-HPETE to leukotrienes.
The enzyme 12-lipoxygenase (ALOX12) catalyzes oxidation of Eicosatetraenoic Acid to 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which may then be metabolized to 12-hydroxyeicosatetraenoic acid (12-HETE) and to hepoxilins.

Eicosatetraenoic Acid is also a precursor to anandamide.
Some Eicosatetraenoic Acid is converted into hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) by epoxygenase.
The production of these derivatives and their actions in the body are collectively known as the "Eicosatetraenoic Acid cascade".

PLA2 activation
PLA2, in turn, is activated by ligand binding to receptors, including:
5-HT2 receptors
mGLUR1
bFGF receptor
IFN-α receptor
IFN-γ receptor
Furthermore, any agent increasing intracellular calcium may cause activation of some forms of PLA2.

PLC activation
Alternatively, Eicosatetraenoic Acid may be cleaved from phospholipids after phospholipase C (PLC) cleaves off the inositol trisphosphate group, yielding diacylglycerol (DAG), which subsequently is cleaved by DAG lipase to yield Eicosatetraenoic Acid.

Receptors that activate this pathway include:
A1 receptor
D2 receptor
α2 adrenergic receptor
5-HT1 receptor
PLC may also be activated by MAP kinase.
Activators of this pathway include PDGF and FGF.

In the body
Cell membranes
Along with other omega−6 and omega−3 fatty acids, Eicosatetraenoic Acid contributes to the structure of cell membranes.
When incorporated into phospholipids, the omega fatty acid affects cell membrane properties, such as permeability and the activity of enzymes and cell-signaling mechanisms.

Brain
Eicosatetraenoic Acid, one of the most abundant fatty acids in the brain, is present in similar quantities to docosahexaenoic acid, with the two accounting for about 20% of brain fatty-acid content.
Eicosatetraenoic Acid is involved in the early neurological development of infants.

CHEMISTRY of EICOSATETRAENOIC ACID:
In chemical structure, Eicosatetraenoic Acid is a carboxylic acid with a 20-carbon chain and four cis-double bonds; the first double bond is located at the sixth carbon from the omega end.
Some chemistry sources define 'arachidonic acid' to designate any of the eicosatetraenoic acids.
However, almost all writings in biology, medicine, and nutrition limit the term to all cis-5,8,11,14-eicosatetraenoic acid.

BIOLOGY of EICOSATETRAENOIC ACID:
Eicosatetraenoic Acid is a polyunsaturated fatty acid present in the phospholipids (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositides) of membranes of the body's cells, and is abundant in the brain, muscles, and liver.
Skeletal muscle is an especially active site of Eicosatetraenoic Acid retention, accounting for roughly 10–20% of the phospholipid fatty acid content typically.
In addition to being involved in cellular signaling as a lipid second messenger involved in the regulation of signaling enzymes, such as PLC-γ, PLC-δ, and PKC-α, -β, and -γ isoforms, arachidonic acid is a key inflammatory intermediate and can also act as a vasodilator.

HISTORY of EICOSATETRAENOIC ACID:
Eicosatetraenoic acid (ETA) is an omega-3 polyunsaturated fatty acid that has garnered significant attention for its nutritional and medicinal benefits.
Historically, Eicosatetraenoic Acid has been present in the diets of indigenous populations, especially those who consumed oily fish and certain marine plants.

These populations exhibited notably lower incidences of inflammatory and cardiovascular diseases, which led to the early recognition of the health-promoting properties of Eicosatetraenoic Acid and related fatty acids.

In traditional remedies, Eicosatetraenoic Acid-rich sources such as fish oil and green-lipped mussel extracts were often employed to alleviate symptoms associated with joint discomfort, arthritis, and skin conditions.
These natural treatments harnessed the anti-inflammatory effects of Eicosatetraenoic Acid, providing relief for ailments that modern science now understands to be influenced by chronic inflammation.

Notably, Eicosatetraenoic Acid's ability to compete with arachidonic acid in metabolic pathways results in the production of less inflammatory mediators, which may explain its traditional use in soothing inflammatory disorders.
Herbalists have long recognized the synergistic effects of combining Eicosatetraenoic Acid-rich oils with other botanicals.

For instance, Eicosatetraenoic Acid has been used alongside herbs such as turmeric, ginger, and boswellia, enhancing the overall anti-inflammatory and analgesic effects of these formulations.
Such combinations are now supported by scientific research, confirming the value of herbal blends that incorporate Eicosatetraenoic Acid for holistic health and wellness.

Overall, eicosatetraenoic acid has made a remarkable contribution to both traditional medicine and modern nutritional science, particularly in supporting joint health, reducing inflammation, and promoting general well-being.
Eicosatetraenoic Acid's legacy continues to inspire the development of effective, natural remedies for a range of health concerns.

PHYSICAL and CHEMICAL PROPERTIES of EICOSATETRAENOIC ACID:
Molecular Weight: 304.5 g/mol
Molecular Formula: C20H32O2
Preferred Name: Arachidonic acid
IUPAC Name: all-cis-5,8,11,14-eicosatetraenoic acid
CAS Number: 506-32-1
EC Number: 208-033-4
Appearance: Colorless oily liquid
Density: 0.922 g/mL at 25 °C
Melting Point: -49 °C
Boiling Point: 169-171 °C

Flash Point: >230 °F
Solubility: Practically insoluble in water; soluble in organic solvents
Log P: 6.9
pKa: 4.75
Refractive Index: 1.50-1.51
Topological Polar Surface Area: 37.3 Å²
Chemical Features:
Functional Groups: Terminal carboxylic acid, multiple cis double bonds
Unsaturation: Four unsaturated bonds → contributes to fluidity and reactivity in biological membranes

Compound Class: Eicosatetraenoic acid (PUFA)
IUPAC Name: (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid
Synonyms: See Synonyms section above
CAS No.: 506-32-1
EC No.: 208-033-4
Molecular Formula: C20H32O2
Molar Mass: 304.47 g/mol
Physical state: viscous liquid
Color: No data available

Odor: No data available
Melting Point: -49 °C
Boiling Point: 169-171 °C
Flash Point: 113 °C - closed cup
Water Solubility: insoluble
Density: 0.922 g/cm3 at 20 °C
Explosive properties: Not classified as explosive
Oxidizing properties: none

Other safety information
No data available
Chemical Formula: C20H32O2
IUPAC Name: icosa-8,11,14,17-tetraenoic acid
InChI Identifier: InChI=1S/C20H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h3-4,6-7,9-10,12-13H,2,5,8,11,14-19H2,1H3,(H,21,22)
InChI Key: HQPCSDADVLFHHO-UHFFFAOYSA-N
Isomeric SMILES: CCC=CCC=CCC=CCC=CCCCCCCC(O)=O
Average Molecular Weight: 304.4669

Monoisotopic Molecular Weight: 304.240230268
Water Solubility: 0.00016 g/L
logP: 6.83
pKa (Strongest Acidic): 4.89
Physiological Charge: -1
Hydrogen Acceptor Count: 2
Hydrogen Donor Count: 1
Polar Surface Area: 37.3 Å²

Rotatable Bond Count: 14
Refractivity: 99.95 m³•mol⁻¹
Polarizability: 38.41 Å³
Number of Rings: 0
Bioavailability: No
Rule of Five: No
Ghose Filter: No
Veber's Rule: No

MDDR-like Rule: No
Chemical Formula: C20H32O2
Molar Mass: 304.474 g·mol−1
Density: 0.922 g/cm3
Melting Point: −49 °C
Boiling Point: 169 to 171 °C
log P: 6.994
Acidity (pKa): 4.752
Molecular Weight: 304.5 g/mol

XLogP3-AA: 5.7
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 2
Rotatable Bond Count: 14
Exact Mass: 304.240230259 Da
Monoisotopic Mass: 304.240230259 Da
Topological Polar Surface Area: 37.3 Å²
Heavy Atom Count: 22

Formal Charge: 0
Complexity: 362
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 4
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

FIRST AID MEASURES of EICOSATETRAENOIC ACID:
-Description of first-aid measures
*General advice:
Show this material safety data sheet to the doctor in attendance.
*If inhaled:
After inhalation:
Fresh air.
*In case of skin contact:
Take off immediately all contaminated clothing.
Rinse skin with
water/ shower.
*In case of eye contact:
After eye contact:
Rinse out with plenty of water.
Call in ophthalmologist.
Remove contact lenses.
*If swallowed:
After swallowing:
Immediately make victim drink water (two glasses at most).
Consult a physician.
-Indication of any immediate medical attention and special treatment needed.
No data available

ACCIDENTAL RELEASE MEASURES of EICOSATETRAENOIC ACID:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains.
Collect, bind, and pump off spills.
Observe possible material restrictions.
Take up dry.
Dispose of properly.
Clean up affected area.

FIRE FIGHTING MEASURES of EICOSATETRAENOIC ACID:
-Extinguishing media:
*Suitable extinguishing media:
Carbon dioxide (CO2)
Foam
Dry powder
*Unsuitable extinguishing media:
For this substance/mixture no limitations of extinguishing agents are given.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of EICOSATETRAENOIC ACID:
-Control parameters:
--Ingredients with workplace control parameters:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use equipment for eye protection.
Safety glasses
*Body Protection:
protective clothing
*Respiratory protection:
Recommended Filter type: Filter A
-Control of environmental exposure:
Do not let product enter drains.

HANDLING and STORAGE of EICOSATETRAENOIC ACID:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed.
Dry.

STABILITY and REACTIVITY of EICOSATETRAENOIC ACID:
-Chemical stability:
The product is chemically stable under standard ambient conditions (room temperature).
-Possibility of hazardous reactions:
No data available