Lipids in Cell Signaling Many of the lipids involved as second messengers in cell signaling pathways arise from the arachidonic acid (AA) pathway. AA is an unsaturated fatty acid that is a normal constituent of membrane phospholipids and is released from the phospholipids by the actions of phospholipase A2 (PLA2). Prostaglandins (PG) arise from a cyclic endoperoxide generated by the enzyme system PG synthetase. This is a complex of enzymes, including cyclooxygenase (COX), required to produce the key intermediate, the cyclic endoperoxide derivative of AA. There is a constitutive (COX-1) and an inducible cyclooxygenase (COX-2). The cyclic endoperoxide is also a precursor of prostacyclin (PGI2) and thromboxane (TXA3). Other groups of compounds in this class, leukotrienes (LT) and lipoxins (LP) are derived directly from AA without the mediation of a cyclic endoperoxide. Lipoxygenase acts on AA to produce 5-hydroperoxyeicosatetraenoic acid (5-HPETE) that is converted to LTA4. LTA4 is the precursor of LTB4, that induces inflammation by its chemotactic and degranulating actions on polymorphonuclear lymphocytes (PML), and of LTC4, LTD4, and LTE4, the amino acid-containing LTs that induce vasoconstriction and bronchoconstriction and are involved in asthma and anaphylaxis. References: Heller, A., et al., Lipid mediators in inflammatory disorders. Drugs, 55, 487-496(1998). Cook, J.A., et al., Prostaglandins, thromboxanes, leukotrienes, and cytochrome P-450 metabolites of arachidonic acid. New Horiz. 1,60-69(1993). Dubois, R.N., et al., Cyclooxygenase in biology and disease. FASEB J. 12, 1063-1073(1998).