Figure 4.

(A) Schematic showing leukotrienes synthesis and signaling (LOX-5 pathway). Free arachidonic acid (Figure 2) is converted into LTA₄ by 5-LOX by activating protein (FLAP). LTA₄ is converted into LTB₄ by LTA₄ hydrolase or LTC₄ by LTC₄ synthase. Gamma-Glutamyl Transferase attaches glutathione to LTC₄ and generates LTD₄. A dipeptidase activity converts LTD₄ into LTE₄. Box under LTB₄ shows its G-protein-coupled receptors BLT1 and BLT2 and ligand preferences and LTB₄ functions. The text box under cysteinyl leukotrienes LTC₄, LYD₄ and LTE₄ indicates receptors CysLT₁ and CysLT₂ with ligand preferences. Downregulation (down) of adenyl cyclase (AC) upregulation (up) of phospholipase C (PLC) coupled to specific G proteins is indicated followed by the cellular effects of cysteinyl LTs. (B). LOX-12 and LOX-15 pathways: Left: Arachidonic acid is metabolized by 12-LOX to 15-hydroperoxyeicosatetraenoic acid/arachidonic acid 15-hydroperoxide (15-HPETE/15-HpETE) or 12(S)-HPETE/12-HPETE. 15-HPETE is further metabolized to yield 15-HETE and lipoxins (specialized pro-resolving mediators). 12-HPETE generates 12-HETE and hepoxilins (anti-inflammatory). Right: Lipoygenase-15 (ALOX15) and ALOX15B generate 15-HETE as the dominant product with a small amount of 12-HETE by ALOX15 activity.