Dpa Biochemistry

1-0-alkyl-2-lysoglycerol 3-phosphocholine (lyso-PAF)

In contrast, synthesis de novo beginning by the acetylation of 1-alkyl-glycero-3-phosphate and finishing by using a cholinephosphotransferase is the primary source of endogenous levels of PAF in cells and blood. PAF is inactivated by removal of its acetyl group by an acetylhydrolase to yield the biologically inactive lyso-PAF. There are two different acetylhydrolases - one in cells and the other in the extracellular (plasma) compartment.

PAF is bound to platelets through a single class of specific receptors (about 250 per cell). Specific receptors have also been documented on many other cell types and it seems likely that most biological responses to PAF are receptor-dependent.

Platelet activating factor is a very potent molecule having biological activity at 5xl0-11M concentrations. Some of its effects are listed in Table 7.2 where it will be seen that this molecule has wideranging effects in many tissues.

In terms of its biochemistry, PAF has general effects on intracellular regulation by increasing Ca2+ uptake and increasing protein phosphorylation via protein tyrosine kinases, protein kinase C and G-protein receptor kinase. It alters inflammatory responses by altering expression of cytokines like tumour necrosis factor-a. Recently, it has been shown to activate immediate-early genes (e.g. c-fos, c-jun) that produce proteins to change other gene expression. PAF also interacts with other biologically active lipids by increasing arachidonate turnover (Section 2.4) and activating the phosphatidylinositol-specific phospholipase C (Section 7.9).

A chemically synthesized derivative of PAF (with a methoxy group at position 2) shows highly selective antitumour properties. Apparently this derivative prevents membrane formation by inhibiting the cytidylyltransferase of the CDP-choline pathway (Section 7.1.5).

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