Eicosanoids or Icosanoids : they are a group of lipid molecules originating from the oxygenation of the essential fatty acids of 20 carbons type ω-3 and ω-6. They serve broad functions as mediators for the central nervous system, inflammation events, and immune response in both vertebrates and invertebrates.
Summary
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- 1 Story
- 2 Biochemistry
- 3 Nomenclature
- 4 Biosynthesis
- 5 References
History
The term was first used by EJ Corey and his collaborators in 1980 , to name a group of molecules that came from a certain fatty acid made up of 20 carbons. Fifty years earlier, in 1930 , gynecologist Raphael Kurzrok and pharmacologist Charles Leib described prostaglandin as a component of semen (prostate prostate) capable of causing the smooth musculature of the uterus to contract. Between 1929 and 1932 , Burr and Burr demonstrated that the elimination of fats from an animal’s diet generates nutritional deficiencies, from where they first described the concept of essential fatty acids . In 1935 ,Ulf von Euler identified prostaglandin . In 1964 Sune Karl Bergström and Bengt Samuelsson linked previous observations by demonstrating that eicosanoids were derived from arachidonic acid , recently considered one of the essential fatty acids and component of phospholipids in the plasma membrane .
In 1971 , Vane found that substances such as aspirin exert their effect by blocking the synthesis of prostaglandins, one of the groupings of eicosanoids 6, Von Euler received the Nobel Prize in medicine in 1970 , and later in 1982 Samuelsson received it , Vane and Bergström. EJ Corey won the Nobel Prize in Chemistry in 1990 , mainly for the synthesis of prostaglandins.
Biochemistry
Two or three molecules produced are derived from each type of molecule grouped within the eicosanoids, either as a result of an essential fatty acid type ω-3 or type ω-6. It will be noted that the metabolic activities of the eicosanoid derivatives depend on their biochemical structure and, generally, their individual structure explains the organic effects of ω-3 and ω-6.
Nomenclature
Chemical structure of 14,15-epoxieicosatrienoic acid, considered an eicosanoid.
An “eicosanoid” (eicosa-, Greek: twenty; see icosahedron) is the general term for oxygenated molecules derived from essential fatty acids all of 20 carbons:
- Eicosapentaenoic acid (EPA) is a 3-3 with five double bonds;
- Arachidonic acid (AA), is a ω-6 with four double bonds;
- Dihomo-gamma-linolenic acid (DGLA), is a ω-6 with three double bonds
Any eicosanoid is denoted by a four-character abbreviation, consisting of:
- Characters 1 and 2. A two-letter abbreviation of the compound’s name (thromboxane = TX).
- Character 3. A letter denoting sequence and not necessarily related to the name of the compound
- Character 4. A subscript representing the number of double bonds in the molecule.
For example
- Prostanoid derivatives of EPA have three double bonds, for example: PGG3, PGH3, PGI3, TXA3, whereas leukotrienes have five: LTB5.
- Prostanoids derived from AA have two double bonds: PGG2, PGH2, PGI2, TXA2, whereas leukotrienes have four: LTB4.
Biosynthesis
The catalytic oxidation of fatty acids is a requirement for the production of eicosanoids, and it takes place thanks to two families of enzymes:
- Cyclooxygenase(COX) types 1, 2 and 3; lead to the formation of prostanoids. Lipoxygenase, in its various forms. 5-lipoxygenase (5-LO) generates leukotrienes.
Mechanisms of action of ω-3:
Eicosanoids from arachidonic acid generally promote the appearance of inflammation. Those of the EPA and the? -Linolenic acid (via DGLA), on the other hand, are generally less inflammatory, or rather inactive and even anti-inflammatory.
Ω-3 and DGLA oppose the inflammatory effects of arachidonic acid (AA) eicosanoids in three ways along the metabolic pathways:
Production of Essential Fatty Acids (EFA) and metabolism for the formation of Eicosanoids. At each step, the ω-3 and ω-6 cascades compete for their enzymes. The figure shows the synthesis of ω-3 and -6 chains, as well as the main eicosanoids of AA, EPA and DGLA.
- Displacement. Dietary ω-3 decreases AA concentrations in tissues and, therefore, reduces inflammatory processes. Animal studies show that increased dietary ω-3 results in decreased AA in the brain and other tissues. Linolenic acid (18: 3 ω-3) contributes to this by displacing linoleic acid (18: 2 ω-6) from the elongase and desaturase enzymes that produce AA. EPA, another ω-3, inhibits the release of AA from the cell membrane by phospholipase A2. It is possible that other mechanisms involving EPA transport have an important role here. But the opposite is also true: Elevating dietary linoleic acid decreases the body’s conversion of α-linolenic acid to EPA. However, the effect is not as potent;
Competitive inhibition: DGLA and EPA compete with AA for access to cyclooxygenase (COX) and lipoxygenase synthesizing enzymes. So the presence of DGLA and EPA in the tissues decreases the production of AA-derived eicosanoids. For example, dietary gamma-linolenic acid (GLA) increases DGLA in tissues and decreases thromboxane TXB2 (a derivative of AA). Similarly, EPA inhibits the production of series 2 PGs and TXs (also derived from AA). Although DGLA does not form LT, a derivative of DGLA blocks the transformation from AA to LT. EPA decreases the formation of AA-derived cysteinyl leukotrienes (Series 4 LTC, LTD, and LTE), forming instead the less active Series 5. Another ω-3 fat, docosahexaenoic acid (DHA) (22: 5 ω-3), it does not produce eicosanoids but it inhibits the formation of prostanoids derived from AA.
Opposition . Certain eicosanoids derived from DGLA and EPA oppose their AA-derived counterparts. For example, DGLA produces PGE1, which powerfully counteracts the arachidonic offspring PGE2. It also produces leukotriene LTB5 which prevents the action of LTB4 derived from AA.
Fish and other marine animals that consume phytoplankton have a high content of ω-3, so that a diet rich in fish tends to decrease inflammatory, cardiovascular, etc. problems. Greenland Eskimos, for example, despite their high fat intake and low carbohydrate intake, have a low incidence of high cholesterol, low-density triglycerides and lipoproteins, and higher high-density lipoprotein values. They suffer less heart problems, and those with heart disease have a low mortality rate (approx. 10%), compared to the North American population (50%). Among Eskimos, there is also a lower incidence of asthma, diabetes, psoriasis and autoimmune diseases, among others.
Metabolic complexity
According to Daniele Piomelli; “It is arguable that the arachidonic acid cascade is the most elaborate of the cellular communication systems that a neurobiologist has to deal with.
Receivers
Each eicosanoid has a specific receptor:
Eicosanoid signaling pathways are complex, making it difficult to characterize the action of a particular eicosanoid. For example, PGE2 binds to four receptors, named EP1-4. Each is encoded by an individual gene, and some exist in various forms (isoforms). Each EP receptor in turn is paired with a G protein. The EP2, EP4 receptor and one of the EP3 isofromas tend to couple with the Gs variety. Doing so increases cyclic AMP and is anti-inflammatory. The EP1 receptor and another isoform of EP3 bind to the Gq protein, increasing intracellular calcium and this is pro-inflammatory. Finally, another isoform of the EP3 receptor binds to the Gi protein, decreasing cAMP and at the same time increasing intracellular calcium.
EPA-derived PGE3 is presumed to have a somewhat different effect on this system, but the characteristics of this are not well understood.