CDP-choline:alkylacetylglycerol cholinephosphotransferase catalyzes the final step in the de novo synthesis of platelet-activating factor.
Platelet-activating factor (PAF) can be synthesized de novo or by a remodeling mechanism involving the sn-2 acyl moiety of alkylacylglycerophosphocholines, a membrane-bound precursor. The final step in the de novo pathway is catalyzed by a dithiothreitol-insensitive cholinephosphotransferase that utilizes 1-alkyl-2-acetyl-sn-glycerol and CDP-choline as substrates. This article reviews various studies concerning the occurrence, assay, subcellular location, biochemical properties, substrate specificity, and regulatory controls of the PAF-related cholinephosphotransferase. Alkylacetylglycerol cholinephosphotransferase, which is located on the cytoplasmic surface of the endoplasmic reticulum, is widely distributed among mammalian tissues. Both the alkyl and acyl analogs of radylacetylglycerol are utilized at equivalent rates. Optimal enzyme activity occurs at pH 8.0 and Mg2+ is required, whereas calcium, deoxycholate, ethanol, and centrophenoxine are inhibitory. Formation of CDP-choline by cytidylyltransferase appears to play a crucial role in the regulation of PAF produced via the cholinephosphotransferase route. Significant differences exist in the behavior of the cholinephosphotransferase activities responsible for the synthesis of PAF and phosphatidylcholine. However, neither enzyme activity has been purified or cloned and, therefore, it is unknown whether a single or two separate proteins are responsible for the observed catalytic activities that form these two distinctly different classes of phospholipids.
Snyder
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Medical Sciences Division, Oak Ridge Associated Universities, TN 37830, USA. fsnyder@compuserve.com
D000818:Animals; D002384:Catalysis; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
D010972:Platelet Activating Factor; D002798:Diacylglycerol Cholinephosphotransferase