Nonclassic eicosanoid
Encyclopedia
Nonclassic eicosanoids are biologically active signaling molecules
made by oxygenation
of twenty-carbon fatty acid
s other than the classic eicosanoid
s.
"Eicosanoid" is the collective
term for oxygenated derivatives of three different 20-carbon essential fatty acids—Eicosapentaenoic acid
(EPA), Arachidonic acid
(AA) and Dihomo-gamma-linolenic acid
(DGLA).
Current usage limits the term to the leukotriene
s (LT) and three types of prostanoid
s—prostaglandin
s (PG) prostacyclin
s (PGI), and thromboxane
s (TX).
However, several other classes can technically be termed eicosanoid, including the hepoxilin
s, resolvins
, isofuran
s, isoprostane
s, lipoxin
s, epi-lipoxin
s, epoxyeicosatrienoic acid
s (EETs) and endocannabinoids.
LTs and prostanoids are sometimes termed 'classic eicosanoids'
in contrast to the 'novel', 'nonclassic' or 'eicosanoid-like' eicosanoids.
The classic eicosanoids are autocrine and paracrine mediators, active at micromolar concentrations (or lower), produced with high stereospecificity. They are produced from EPAs (chiefly AA) from either cyclooxygenase
(COX) or 5-lipoxygenase
.
Broadly, the nonclassic eicosanoids are the products of 20-carbon EFAs and
Also included are
Lipid signaling
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses...
made by oxygenation
Oxygenation
Oxygenation may refer to:* Oxygenation , a measurement of dissolved oxygen concentration in soil or water* Oxygenation , the process by which concentrations of oxygen increase within a tissue...
of twenty-carbon fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s other than the classic eicosanoid
Eicosanoid
In biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, ....
s.
Terminology
"Eicosanoid" is the collective
term for oxygenated derivatives of three different 20-carbon essential fatty acids—Eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...
(EPA), Arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
(AA) and Dihomo-gamma-linolenic acid
Dihomo-gamma-linolenic acid
Dihomo-γ-linolenic acid is a 20-carbon ω−6 fatty acid. In physiological literature, it is given the name 20:3 . DGLA is a carboxylic acid with a 20-carbon chain and three cis double bonds; the first double bond is located at the sixth carbon from the omega end. DGLA is the elongation product...
(DGLA).
Current usage limits the term to the leukotriene
Leukotriene
Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
s (LT) and three types of prostanoid
Prostanoid
Prostanoid is the term used to describe a subclass of eicosanoids consisting of: the prostaglandins , the thromboxanes and the prostacyclins - Biosynthesis : Cyclooxygenase catalyzes the conversion of the free essential fatty acids to...
s—prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
s (PG) prostacyclin
Prostacyclin
Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...
s (PGI), and thromboxane
Thromboxane
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....
s (TX).
However, several other classes can technically be termed eicosanoid, including the hepoxilin
Hepoxilin
Hepoxilins are nonclassic eicosanoid hormones involved in inflammation.-Biochemistry:They derive from arachidonic acid via oxidation by the enzyme 12-lipoxygenase...
s, resolvins
Resolvins
Resolvins are compounds that are made by the human body from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid . They are produced by the COX-2 pathway especially in the presence of aspirin...
, isofuran
Isofuran
Isofurans are nonclassic eicosanoids formed nonenzymatically by free radical mediated peroxidation of arachidonic acid. The isofurans are similar to the isoprostanes and are formed under similar conditions, but contain a substituted tetrahydrofuran ring...
s, isoprostane
Isoprostane
The isoprostanes are prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidationof essential fatty acids without the direct action of cyclooxygenase enzyme....
s, lipoxin
Lipoxin
Lipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation....
s, epi-lipoxin
Epi-lipoxin
Epi-lipoxins are the 5R-epimers of lipoxins.These nonclassic eicosanoids are formed in vivo, in the presence of aspirin. They play a counter-regulatory role in inflammation, serving as a stop signal....
s, epoxyeicosatrienoic acid
Epoxyeicosatrienoic acid
The Epoxyeicosatrienoic acids or EETs are signaling molecules formed by the action of Cytochrome P450 epoxygenase on 20-carbon essential fatty acids, such as arachidonic acid, from which it is produced by the enzyme epoxygenase....
s (EETs) and endocannabinoids.
LTs and prostanoids are sometimes termed 'classic eicosanoids'
in contrast to the 'novel', 'nonclassic' or 'eicosanoid-like' eicosanoids.
The classic eicosanoids are autocrine and paracrine mediators, active at micromolar concentrations (or lower), produced with high stereospecificity. They are produced from EPAs (chiefly AA) from either cyclooxygenase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
(COX) or 5-lipoxygenase
Lipoxygenase
Lipoxygenases are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:...
.
Broadly, the nonclassic eicosanoids are the products of 20-carbon EFAs and
- Other oxygenation enzymes, (hepoxilinHepoxilinHepoxilins are nonclassic eicosanoid hormones involved in inflammation.-Biochemistry:They derive from arachidonic acid via oxidation by the enzyme 12-lipoxygenase...
s, resolvinsResolvinsResolvins are compounds that are made by the human body from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid . They are produced by the COX-2 pathway especially in the presence of aspirin...
, lipoxinLipoxinLipoxins are a series of anti-inflammatory mediators. Lipoxins are short lived endogenously produced nonclassic eicosanoids whose appearance in inflammation signals the resolution of inflammation....
s, epi-lipoxinEpi-lipoxinEpi-lipoxins are the 5R-epimers of lipoxins.These nonclassic eicosanoids are formed in vivo, in the presence of aspirin. They play a counter-regulatory role in inflammation, serving as a stop signal....
s, epoxyeicosatrienoic acidEpoxyeicosatrienoic acidThe Epoxyeicosatrienoic acids or EETs are signaling molecules formed by the action of Cytochrome P450 epoxygenase on 20-carbon essential fatty acids, such as arachidonic acid, from which it is produced by the enzyme epoxygenase....
s (EETs)); - Uncatalyzed oxygenation reactions, (isofuranIsofuranIsofurans are nonclassic eicosanoids formed nonenzymatically by free radical mediated peroxidation of arachidonic acid. The isofurans are similar to the isoprostanes and are formed under similar conditions, but contain a substituted tetrahydrofuran ring...
s, isoprostaneIsoprostaneThe isoprostanes are prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidationof essential fatty acids without the direct action of cyclooxygenase enzyme....
s, phytoprostanes); - Addition reactions other than oxygenation (endocannabinoids).
Also included are
- Side products from the classic eicosanoid biosynthesis, (levuglandinLevuglandinLevuglandins are reactive aldehydes formed by the spontaneous rearrangement of prostaglandin H . Enantiomerically pure levuglandin E2 can also be formed through the cyclooxygenase pathway by a rearrangement of the prostaglandin endoperoxide PGH 2. They are nonclassic eicosanoids...
s, OxoeicosanoidOxoeicosanoidThe oxoeicosanoids are nonclassic eicosanoids, derived from arachidonic acid .Lipoxygenase produces 5-HETE from AA; a dehydrogenase produces oxoeicosanoids from 5-HETE....
s); - Reactions between other fatty acids and these pathways (the COX products of pinolenicPinolenic acidPinolenic acid is a fatty acid contained in the Korean Pine nut and the seeds of other conifers . The highest percentage of pinolenic acid is found in Siberian pine nuts and the oil produced by them....
and mead acidMead acidMead acid is an omega-9 fatty acid, first characterized by James F. Mead. Like some other omega-9 polyunsaturated fatty acids animals can make Mead acid de novo. Its elevated presence in the blood is an indication of essential fatty acid deficiency...
).