Leukotriene Synthesis

Arachidonic acid is converted to a variety of linear hydroperoxy (–OOH) acids by a separate pathway involving a family of lipoxygenases (LOX).
For example, 5-LOX converts arachidonic acid to 5-hydroperoxy-6,8,11,14 eicosatetraenoic acid ([5-HPETE]; Fig. 1). 5-HPETE is converted to a series of LT containing four double bonds, the nature of the final products varying according to the tissue. LT are mediators of allergic response and inflammation. Inhibitors of 5-LOX and LT-receptor antagonists are used in the treatment of asthma. [Note: LT synthesis is inhibited by cortisol and not by NSAID. Aspirin-exacerbated respiratory disease is a response to LT overproduction with NSAID use in ~10% of individuals with asthma.]

Figure 1:  Overview of the biosynthesis and function of some important prostaglandins (PG), leukotrienes (LT), and a thromboxane (TX) from arachidonic acid. [Note: The arachidonic acid in the membrane phospholipid was derived from the ω-6 essential fatty acid (FA), linoleic, also an ω-6 FA.] PI = phosphatidylinositol; NSAID = nonsteroidal anti-inflammatory drugs; Glu = glutamate; Cys = cysteine; Gly = glycine.