Leukotriene A4 (LTA4) is synthesized in mast cells, eosinophils, and neutrophils from arachidonic acid by 5-lipoxygenase (5-LO), which exhibits both lipoxygenase and LTA4 synthase activities.1,2 LTA4 is rapidly metabolized by LTA4 hydrolase or LTC4 synthase to LTB4 or LTC4, respectively.2 LTA4, from leukocytes, is known to undergo transcellular metabolism in platelets, erythrocytes, and endothelial cells.3 Further metabolism of LTA4 by 15-LO leads to lipoxin biosynthesis.2 LTA4 as a free acid is highly unstable. The methyl ester is stable and can be readily hydrolyzed to the free acid as needed.
1
Shimizu, T., Rådmark, O., and Samuelsson, B. Enzyme with dual lipoxygenase activities catalyzes leukotriene A4 synthesis from arachidonic acid. Proc Natl Acad Sci USA81689-693(1984).
2
Samuelsson, B., Dahlén, S., Lindgren JÅ, et al. Leukotrienes and lipoxins: Structures, biosynthesis, and biological effects. Science2371171-1176(1987).
3
Maclouf, J.A., and Murphy, R.C. Transcellular metabolism of neutrophil-derived leukotriene A4 by human platelets. A potential cellular source of leukotriene C4. J Biol Chem263174-181(1988).
Samuelsson, B., Dahlén, S., Lindgren JÅ, et al. Leukotrienes and lipoxins: Structures, biosynthesis, and biological effects. Science2371171-1176(1987).
Shimizu, T., Rådmark, O., and Samuelsson, B. Enzyme with dual lipoxygenase activities catalyzes leukotriene A4 synthesis from arachidonic acid. Proc Natl Acad Sci USA81689-693(1984).
Manganaro, F., Gaudette, Y., Pombo-Gentile, A., et al. Purification and characterization of leukotriene A4 epoxide hydrolase from dog lung. Prostaglandins36859-874(1988).
Maclouf, J.A., and Murphy, R.C. Transcellular metabolism of neutrophil-derived leukotriene A4 by human platelets. A potential cellular source of leukotriene C4. J Biol Chem263174-181(1988).