Leukotriene synthesis

Leukotriene synthesis and effects

Leukotrienes are other important mediators involved in the inflammatory response.

Mediators that are derived from phospholipids are the so-called eicosanoids, which can be divided into two groups: the prostanoids (prostaglandins and tromboxanes) and leukotrienes. Arachidonic acid is the starting point for both groups.

When arachidonic acid is converted by 5-lipo-oxygenase, the pathway of leukotrienes is entered.

LTB4 is the predominant leukotriene involved in the activation of immune cells and chemotaxis. The cysteinyl-leukotrienes (LTE4, LTC4, LTD4 and LTF4) cause bronchospasms (involved in asthma), vasoconstriction of most blood vessels, especially of the coronaries.

Drug targets in leukotriene synthesis

Drug targets in leukotriene synthesis

Different drugs interfere in the metabolic pathway of leukotrienes:

  • Glucocorticosteroids inhibit (indirectly) the phospholipase 2 (PLA2) activity.
  • 5-lipoxygenase inhibitors such as zileuton inhibit the two initial steps in leukotriene synthesis and decrease the amounts of 5-HPETE and LTA4.
  • adenosine is able to inhibit the synthesis of LTB4.
  • Leukotriene antagonists such as montelukast and zafirlukast antagonize leukotrienes at their receptors.