Enzymes of platelet activating factor synthesis in brain.
In this review, evidence is summarized for the production of PAF in brain, in response to stimulation associated with pathology. As well, there is a growing literature on the duality of actions of this lipid autocoid upon nervous tissue, indicated by extracellular and intracellular actions and binding sites for PAF in brain. The metabolic routes to PAF can be divided into the de novo and remodelling pathways of synthesis. The de novo route consists of 1-alkyl glycerophosphate acetyltransferase, and the subsequent actions of distinct phosphohydrolase and cholinephosphotransferase activities. This acetyltransferase can be activated by phosphorylation, and inhibited by MgATP and fatty acyl CoA thioesters, inhibitions which have particular relevance to brain ischemia. There is also evidence that the cholinephosphotransferase is controlled by phosphorylation, and regulated by levels of CDP-choline. The remodelling pathway to PAF relies upon the actions of phospholipase A2 or CoA-independent transacylases to generate the 1-alkyl glycerophosphorylcholine, as substrate for a distinct acetyltransferase. Following stimulation, rising intracellular calcium may trigger arachidonate selective cytosolic phospholipase activity which leads to increased PAF synthesis. The 1-alkyl glycerophosphocholine acetyltransferase activity is quite small in brain in comparison with the de novo acetyltransferase activity, and is also controlled by phosphorylation. Evidence has been presented for the actions of both pathways in brain, in response to biologically relevant stimulation pertinent to the disease state.
Baker
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RR
Department of Medicine, University of Toronto, Canada.
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism; D006801:Humans; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000096:biosynthesis*
D010972:Platelet Activating Factor; D000123:Acetyltransferases; C052591:alkylglycerophosphate 2-O-acetyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D010741:Phospholipases A; D054467:Phospholipases A2; D010744:Phosphoric Monoester Hydrolases