Eicosanoid Biosynthesis

Abstract

Eicosanoids are the major products derived from the cellular metabolism of arachidonic acid by the enzymes cyclooxygenase, lipoxygenase and epoxygenases. The eicosanoids comprise several compounds, which include prostaglandins, thromboxanes, prostacyclins, leukotrienes, lipoxins and epoxyeicosatrienoic acids. They represent the major group of metabolically active lipids, exerting their functions through different mechanisms, that is by receptor binding and intracellular signalling pathway modulation. Their effects are diverse, acting on every cell of the body, with a short half‐life. A tight regulation on the processes of formation and inactivation or clearance is fundamental to prevent the exacerbation of their effects. Although initially they were strictly linked to inflammatory processes, recent evidences point out their homeostatic counterpart. Thus, there are eicosanoids involved in vasoconstriction/vasodilatation balance, thrombotic/antithrombotic balance and inflammation/anti‐inflammation balance. This article will focus on the enzymes involved in the formation of these lipids.

Key concepts:

  • Eicosanoids are important lipid mediators involved in cellular homeostasis.

  • Most eicosanoid effects are mediated through specific receptors.

  • Inhibition or activation of the key enzymes involved in the biosynthesis of eicosanoids has encouraged the development of new therapeutics approaches.

Keywords: prostaglandins; leukotrienes; prostanoids; prostacyclins; thromboxanes; epoxyeicosatrienoic acids

Figure 1.

An outline of the eicosanoid pathway. The arachidonyl residue in the sn‐2 position of a phospholipid becomes substrate for the COX, LOX and CYP branch enzymes after PLA2 action.

Figure 2.

The COX branch. Each final compound is the result of specific synthesising enzymes acting on the same substrate PGG2. Abbreviations in the text.

Figure 3.

The LOX branch. The leukotrienes are the compounds derived from the action of 5‐lipoxygenase on arachidonic acid. LTA4 is the precursor of both LTB4, mainly involved in neutrophil function, and LTC4, from which derive LTD4 and LTE4. Lipoxins A and B (LXA and LXB) exert their functions in the vascular system and in the cells of the immune system.

Figure 4.

The CYP branch. Different AA epoxygenases carry out the addition of an oxygen atom to the double bond in a selective way. The EETs are then inactivated by the action of epoxide hydrolases.

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Fernandez, Ana Z, Fatima Garces, Maria, Alvarado‐Castillo, Claudia P, and Estrada, Omar(Apr 2010) Eicosanoid Biosynthesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001392.pub2]