In biochemistry, eicosanoids are a class of oxygenated hydrophobic molecules that largely function as autocrine and paracrine mediators. Eicosanoids derive from 20-carbon polyunsaturated essential fatty acids, most commonly arachidonic acid (AA) in humans. The IUPAC and the IUBMB use the equivalent term Icosanoid.

Nomenclature

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The prefix eicosa- or icosa- (from the Greek for twenty; see icosahedron) denotes the number of carbon atoms in arachidonic acid. The term "eicosanoids" is used as a collective name for molecules derived from 20-carbon fatty acids. Current usage limits this to the leukotrienes and prostanoids, but several other classes are technically eicosanoid, including the resolvins, isofurans, isoprostanes, lipoxins, epoxyeicosatrienoic acids (EETs), neuroprotectin D and some endocannabinoids.

The numbering of eicosanoids is used to denote the number of double bonds. The AA-derived prostanoids have two, while the leukotrienes have four.

See more detail at Essential Fatty Acid Interactions - Nomenclature

Synthesis

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The first step of eicosanoid biosynthesis is the release from phospholipids (by phospholipase A₂) or diacylglycerol (by phospholipase C) of a 20-carbon essential fatty acid (EFA) containing three, four, or five double bonds, (the ω-6 DGLA, ω-6 AA or ω-3 EPA, respectively). Most human eicosanoids derive from AA. This EFA has two possible eicosanoid fates:

• 5-lipoxygenase pathway:
  • Leukotrienes
• Cyclooxygenase pathway ("prostanoids"):
  • Prostaglandins
  • Prostacyclin
  • Thromboxanes

Leukotrienes

5-lipoxygenase uses the nuclear-membrane protein cofactor 5-lipoxygenase-activating protein (FLAP) to sequentially convert arachidonic acid, first into 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and then 5-HPETE into leukotriene A4 (LTA4). LTA4 may be converted into LTB4 by the enzyme leukotriene A4 epoxide hydrolase. Eosinophils, mast cells, and alveolar macrophages use the enzyme leukotriene C4 synthase to conjugate glutathione with LTA4 to make leukotriene C4 (LTC4). LTC4 is transported out of the cell, where a glutamic acid moiety is removed from it to make leukotriene D4 (LTD4). LTD4 is cleaved by dipeptidases to make leukotriene E4 (LTE4).

LTC4, LTD4 and LTE4 all contain cysteine and are collectively known as the cysteinyl leukotrienes.

Prostanoids

All prostanoids originate from prostaglandin H (PGH, as PGH₁, PGH₂, or PGH₃), which is converted by different enzymes into the various compounds. The enzyme PGH2-synthase is in fact a combination of a peroxidase and a cyclooxygenase (Cox-1 or Cox-2). The Cox enzymes are the molecular target of the NSAIDs, such as aspirin (see below).

PGH is converted:

• By PGE synthetase into PGE (which in turn is converted into PGF)
• By PGD synthetase into PGD
• By Prostacyclin synthase into prostacyclin (PGI2)
• By Thromboxane synthase into thromboxanes

Receptors

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There are specific receptors for all eicosanoids (see also specific articles):

• Leukotrienes:
  • CysLT1 (Cysteinyl leukotriene receptor type 1)
  • CysLT2 (Cysteinyl leukotriene receptor type 2)
  • BLT1 (Leukotriene B4 receptor)
• Prostanoids:
  • PGD₂: DP-(PGD₂)
  • PGE₂:
    • EP₁-(PGE₂)
    • EP₂-(PGE₂)
    • EP₃-(PGE₂)
    • EP₄-(PGE₂)
  • PGF_2α: FP-(PGF_2α)
  • PGI₂ (prostacyclin): IP-(PGI₂)
  • TXA₂ (thromboxane): TP-(TXA₂)

Function and pharmacology

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Leukotrienes

Leukotrienes play an important role in inflammation, especially as part of the Slow Reacting Substance of Anaphylaxis, and blocking leukotriene receptors can play a role in the management of inflammatory diseases such as asthma (montelukast, zafirlukast), psoriasis, and rheumatoid arthritis.

Prostanoids

Main articles: Prostaglandin, Prostacyclin and Thromboxane.

Prostanoids mediate local symptoms of inflammation: vasoconstriction or vasodilation, coagulation, pain and fever. Inhibition of cyclooxygenase, specifically the inducible COX II isoform, is the hallmark of NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin. COX II is responsible for pain and inflammation, while COX I is responsible for platelet clotting actions.

References

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1. (in .pdf format)
3. Dr M.W. King's biochemistry page

Eicosanoids

Eïcosanoïde | eicosanoid | Eikozanoidy