Properties and regulation of microsomal PAF-synthesizing enzymes in rat brain cortex

Platelet-activating factor (PAF) is a phospholipid mediator of long-term po tentiation, synaptic plasticity and memory formation as well as of the deve lopment of brain damage. In brain, PAF is synthesized by two distinct pathw ays but their relative contribution to its productions, in various physiolo gical and pathological conditions, is not established. We have further inve stigated on the properties of the two enzymes that catalyze the last step o f the de novo or remodeling pathways in rat brain microsomes, PAF-synthesiz ing phosphocholinetransferase (PAF-PCT) and lysoPAF acetyltransferase (lyso PAF-AT), respectively. The latter enzyme is fully active at mu M Ca2+ conce ntration, inhibited by MgATP and activated by phosphorylation. Because the reversibility of the reaction catalyzed by PAF-PCT, its direction depends o n the ratio [CDP-choline]/[CMP], which is related to the energy charge of t he cell. These and other properties indicate that the de novo pathway shoul d mainly contribute to PAF synthesis for maintaining its basal levels under physiological conditions. The remodeling pathway should be more involved i n the production of PAF during ischemia. During reperfusion, the overproduc tion of PAF should be the result of the concomitant activation of both path ways.