Properties and regulation of microsomal PAF-synthesizing enzymes in rat brain cortex.
Platelet-activating factor (PAF) is a phospholipid mediator of long-term potentiation, synaptic plasticity and memory formation as well as of the development of brain damage. In brain, PAF is synthesized by two distinct pathways but their relative contribution to its productions, in various physiological and pathological conditions, is not established. We have further investigated on the properties of the two enzymes that catalyze the last step of the de novo or remodeling pathways in rat brain microsomes, PAF-synthesizing phosphocholinetransferase (PAF-PCT) and lysoPAF acetyltransferase (lysoPAF-AT), respectively. The latter enzyme is fully active at microM Ca2+ concentration, inhibited by MgATP and activated by phosphorylation. Because the reversibility of the reaction catalyzed by PAF-PCT, its direction depends on the ratio [CDP-choline]/[CMP], which is related to the energy charge of the cell. These and other properties indicate that the de novo pathway should mainly contribute to PAF synthesis for maintaining its basal levels under physiological conditions. The remodeling pathway should be more involved in the production of PAF during ischemia. During reperfusion, the overproduction of PAF should be the result of the concomitant activation of both pathways.
Francescangeli
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Istituto di Biochimica e Chimica Medica, Università di Perugia, Italy.
Boila
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Goracci
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D000123:Acetyltransferases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology*; D002798:Diacylglycerol Cholinephosphotransferase / Q000378:metabolism*; D004789:Enzyme Activation; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010972:Platelet Activating Factor; D000255:Adenosine Triphosphate; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D002118:Calcium