There is a wide variety of fatty acids found in nature. Two classes of fatty acids are considered essential, the

omega-3 Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their ...

and

omega-6 Omega−6 fatty acids (also referred to as ω−6 fatty acids or ''n''−6 fatty acids) are a family of polyunsaturated fatty acids (PUFA) that share a final carbon-carbon double bond in the ''n''−6 position, that is, the sixth bond, count ...

fatty acids. Essential fatty acids are necessary for humans but cannot be synthesized by the body and must therefore be obtained from food. Omega-3 and omega-6 are used in some cellular signaling pathways and are involved in mediating

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

, protein synthesis, and

metabolic pathways In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical ...

in the human body.

Arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

(AA) is a 20-carbon omega-6 essential fatty acid. It sits at the head of the "arachidonic acid cascade," which initiates 20 different

signalling pathways Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term ...

that control a wide array of biological functions, including

cell growth Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

, and the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. Most AA in the human body is derived from dietary

linoleic acid Linoleic acid (LA) is an organic compound with the formula . Both alkene groups () are ''cis''. It is a fatty acid sometimes denoted 18:2 (n−6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid. Linoleic acid is a polyunsat ...

(18:2 ω-6), which is found in

nuts Nut often refers to: * Nut (fruit), fruit composed of a hard shell and a seed * Nut (food), a dry and edible fruit or seed, including but not limited to true nuts * Nut (hardware), fastener used with a bolt Nut, NUT or Nuts may also refer to: A ...

seeds In botany, a seed is a plant structure containing an embryo and stored nutrients in a protective coat called a ''testa''. More generally, the term "seed" means anything that can be sown, which may include seed and husk or tuber. Seeds are the ...

vegetable oil Vegetable oils, or vegetable fats, are oils extracted from seeds or from other parts of edible plants. Like animal fats, vegetable fats are ''mixtures'' of triglycerides. Soybean oil, grape seed oil, and cocoa butter are examples of seed ...

s, and

animal fat Animal fats are lipids derived from animals which are used by the animal for a multitude of functions, or can be used by humans for dietary, sanitary, and cosmetic purposes. Depending on the temperature of the fat, it can change between a solid s ...

Eicosanoid series nomenclature

Eicosanoids are signaling molecules derived from the essential fatty acids (EFAs). They are a major pathway by which the EFAs act in the body. There are four classes of eicosanoid and two or three series within each class. The plasma membranes of

cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...

contain

phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s, composed of a hydrophilic phosphate head and two hydrophobic

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

tails. Some of these fatty acids are 20-carbon polyunsaturated essential fatty acids (AA, EPA, or DGLA). EFAs are cleaved out of the phospholipid and released as free fatty acids. The EFA is oxygenated (by either of two pathways) and further modified, yielding the eicosanoids. After oxidation, the eicosanoids are further modified, making a ''series''. Members of a series are differentiated by a letter and are numbered by the number of double bonds, which does not change within a series. For example, cyclooxygenase action upon AA (with 4 double bonds) leads to the series-2

thromboxanes Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring. Thromboxane is named for it ...

(TXA₂, TXB₂... ), each with two double bonds. Cyclooxygenase action on EPA (with 5 double bonds) leads to the series-3 thromboxanes (TXA₃, TXB₃, etc.), each with three double bonds. There are exceptions to this pattern, some of which indicate

stereochemistry Stereochemistry, a subdiscipline of chemistry, studies the spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoisomers, which are defined ...

(PGF_2α). Table (1) shows these sequences for AA (20:4 ω-6). The sequences for EPA (20:5 ω-3) and DGLA (20:3 ω-6) are analogous. All prostanoids are substituted prostanoic acids. Cyberlipid Center's Prostenoid page illustrates the parent compound and the rings associated with each series letter. The

IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...

and the IUBMB use the equivalent term icosanoid.

The arachidonic acid cascade in the Central Nervous System

The arachidonic acid cascade proceeds somewhat differently in the

(CNS).

Neurohormone A neurohormone is any hormone produced and released by neuroendocrine cells (also called neurosecretory cells) into the blood. By definition of being hormones, they are secreted into the circulation for systemic effect, but they can also have a ro ...

neuromodulator Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a secon ...

s, or

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s act as first messengers. They activate phospholipids to release AA from

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

cell membranes as a free fatty acid. During its short lifespan, free AA may affect the activity of the neuron's

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s and

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a f ...

s. Or it may be metabolized to form eicosanoids,

epoxyeicosatrienoic acid The epoxyeicosatrienoic acids or EETs are signaling molecules formed within various types of cells by the metabolism of arachidonic acid by a specific subset of cytochrome P450 enzymes, termed cytochrome P450 epoxygenases. They are nonclassic e ...

s (EETs),

neuroprotectin Protectin D1 also known as neuroprotectin D1 (when it acts in the nervous system) and abbreviated most commonly as PD1 or NPD1 is a member of the class of specialized proresolving mediators. Like other members of this class of polyunsaturated fat ...

D, or various

endocannabinoids Cannabinoids () are several structural classes of compounds found primarily in the ''Cannabis'' plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoact ...

(

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

and its analogs). The actions of eicosanoids within the brain are not as well characterized as they are in inflammation. Studies suggest that they act as

second messengers Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...

within the neuron, possibly controlling presynaptic inhibition and the activation of

C. They also act as paracrine mediators, acting across synapses to nearby cells. The effects of these signals are not well understood. Daniele Piomelli has commented:

Neurons in the CNS are organized as interconnected groups of functionally related cells (e.g. in sensory systems). A diffusible factor released from a neuron into the
interstitial fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the Cell (biology), cells of any multicellular organism. Body water, Total body water in healthy adults is about 50–60% (range 45 to 75%) of total body weight; women ...
, and able to interact with membrane receptors on adjacent cells would be ideally used to "synchronize" the activity of an ensemble of interconnected neural cells. Furthermore, during development and in certain forms of learning, postsynaptic cells may secrete regulatory factors that diffuse back to the presynaptic component, determining its survival as an active terminal, the amplitude of its sprouting, and its efficacy in secreting neurotransmitters—a phenomenon known as retrograde regulation. Studies have proposed that arachidonic acid metabolites participate in retrograde signaling and other forms of local modulation of neuronal activity.

Further discussion

Figure 2 shows two pathways from EPA to DHA, including the exceptional Sprecher's shunt. 5-LO acts at the fifth carbon from the

carboxyl group In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl group (e.g. ...

. Other lipoxygenases—8-LO, 12-LO, and 15-LO—make other eicosanoid-like products. To act, 5-LO uses the nuclear-membrane

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

5-lipoxygenase-activating protein Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ''ALOX5AP'' gene. Function FLAP is necessary for the activation of 5-lipoxygenase and theref ...

(FLAP), first to a hydroperoxyeicosatetraenoic acid (HPETE), then to the first leukotriene, LTA.

References

{{Reflist, 30em Docosanoids Eicosanoids Fatty acids Immune system ca:Àcids grassos essencials#Interacció d'àcids grassos essencials

Eicosanoid series nomenclature

The arachidonic acid cascade in the Central Nervous System

Further discussion

See also

References