Plateletactivating Factor

Chemistry and Biosynthesis

PAF is 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine. Its structure is:

cr ch3

PLATELET-ACTIVATING FACTOR (n = 11 to 17)

PAF contains a long-chain alkyl group joined to the glycerol backbone in an ether linkage at position 1 and an acetyl group at position 2. PAF actually represents a family of phospholipids because the alkyl group at position 1 can vary in length from 12 to 18 carbon atoms. In human neutrophils, PAF consists predominantly of a mixture of the 16- and 18-carbon ethers, but its composition may change when cells are stimulated.

Like the eicosanoids, PAF is not stored in cells but is synthesized in response to stimulation. The major pathway by which PAF is generated involves the precursor 1-O-alkyl-2-acyl-glycerophosphocholine, a lipid found in high concentrations in the membranes of many types of cells. The 2-acyl substituents include AA. PAF is synthesized from this substrate in two steps (Figure 25-3). The first involves the action of phospholipase A2, the initiating enzyme for eicosanoid biosynthesis, with the formation of 1-O-alkyl-2-lyso-glycerophosphocholine (lyso-PAF) and a free fatty acid (usually AA). Eicosanoid and PAF biosynthesis thus is closely coupled. The second, rate-limiting step is performed by the acetylcoenzyme-A-lyso-PAF acetyltransferase. PAF synthesis also can occur de novo; a phosphocholine substituent is transferred to alkyl acetyl glycerol by a distinct lysoglycerophosphate acetylcoenzyme-A transferase. This pathway may contribute to physiological levels of PAF for normal cellular functions. The synthesis of PAF may be stimulated during antigen-antibody reactions or by a variety of agents, including chemotactic peptides, thrombin, collagen, and other autacoids; PAF also can stimulate its own formation. Both

| l-O-alkyl-2-acyl-glycerophosphocholine |

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