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Eicosanoid

In biochemistry, eicosanoids are a class of oxygenated hydrophobic hormones that largely function as paracrine mediators. All eicosanoids derive from arachidonic acid, itself a fatty acid derivative.

Nomenclature

Eicosa (Greek: twenty, see eicosahedron) denotes the amount of C atoms in arachidonic acid. The numbering of eicosanoids is used to denote the number of double bonds. The prostanoids generally have two, while the leukotrienes have four.

Synthesis

The first step of eicosanoid biosynthesis is the release of arachidonic acid from phospholipids or diacylglycerol by phospholipase, a membrane-bound protein that responds to external stimuli.

Arachidonic acid has two possible fates:

• Leukotrienes
• Cyclooxygenase pathway ("prostanoids"):
  • Prostaglandins
  • Prostacyclin
  • Thromboxane

Leukotrienes

Lipooxygenase converts arachidonic acid into HPETEs (hydroxyperoxyeicosatetraenoic acids), which converts into leukotriene A4 (LTA4). LTA4 is converted into LTB4 by addition of H₂O or conjugated with glutathione to form leukotriene D4 (LTD4). LTD4, in turn, is converted into LTE4. Of the leukotrienes, LTA4 en LTD4 are most important.

Prostanoids

All prostanoids originate from prostaglandin H2 (PGH2), 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).

PGH2 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 thromboxane

Function and pharmacology

Receptors

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

• Leukotrienes:
  • to be filled in
• 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)

Leukotrienes

Leukotrienes play an important role in inflammation, and blocking leukotriene receptors can play a role in the management of asthma (montelukast, zafirlukast).

Prostanoids

See also the main article prostaglandin

Prostanoids mediate local symptoms of inflammation: vasoconstriction or vasodilation, coagulation, pain and fever. Inhibition of cyclooxygenase is the hallmark of NSAIDs (non-steroidal anti-inflammatory drugs), such as aspirin.