Degradation of Platelet-Activating Factor in Brain

Platelet-activating factor (PAF), a phospholipid mediator of inflammation, is rapidly synthesized by neural (neurons and glial cells) and nonneural cells in response to neurotransmitters (glutamate and its analogs), cytokines (tumor necrosis factor-α, interferon-γ, interleukin-1), and pathological situations (Sogos et al., 1990; Prescott et al., 2000; Karasawa et al., 2003; Kunievsky and Yavin, 1994). PAF is normally present in the mammalian tissues in picomolar concentrations, and is found both in the cytosol and body fluids including blood plasma, cerebrospinal fluid, urine, and amniotic fluid (Lynch and Hensen, 1986; Cox et al., 1981; Billah et al., 1983). PAF is not stored in cells. Its levels in brain, other body tissues, and plasma are modulated by PAF-acetyl hydrolases. This enzyme inactivates PAF by removing the acetyl group from the sn-2 position of glycerol moiety and generating lyso-PAF, which is biologically inactive (Fig. 8.1). The lyso-PAF can be reacylated by an acyl-CoA/1-radyl-sn-glycero-3-phosphocholine acyltransferase. Alkyl-PAF is less potent than PAF. The alkyl moiety of lyso-PAF is degraded to an aldehyde by a tetrahydropiridine-dependent alkyl monooxygenase (Lee et al., 1981). Alternatively, a lysophospholipase D (lyso-PLD) can hydrolyze phosphocholine moiety to generate an analog of phosphatidic acid, or catalyze a phosphate transfer by a transphosphatidylation reaction (Wykle and Schremmer, 1974).


Catalytic Subunit High Density Lipoprotein Serine Esterase Factor Acetylhydrolase Intracellular Type 
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