Leukotriene LTA4, biosynthesis

The cellular locations of leukotriene biosynthesis are determined by the distribution and location of the enzymes needed for their production. 5-Lipoxygenase is found in only a limited number of specific cell types, predominantly of myeloid extraction. Because of this restricted expression, production of LTA4 is largely limited to those cells (e.g., basophils, eosinophils, neutrophils, macrophages, mast cells, and monocytes) (66). These cells produce LTA4, further process it to either LTB4 or LTC4, or secrete it. 

It is clear that 5-lipoxygenase (5-LO) [EC 1.13.11.34], through a two-step process, is the enzyme responsible for the production of LTA4. Thus the mechanism of action and, to a lesser extent, the structure of 5-LO have largely influenced the design and discovery of inhibitors of leukotriene biosynthesis. This enzyme has been the subject of intense research since its discovery, as discussed below (Section 5.1), and many inhibitors have been described. 

Figure 3 Cellular biosynthesis of leukotriene B4. AA, arachidonic acid FLAP, 5-lipoxygenase-activating protein 5-LO,5-lipoxygenase CPLA2, cytosolic phospholipase A2 A4H, LTA4 hydrolase PLs, phospholipids LysoPLs, lysophospholipids.

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