MGATP INHIBITS THE SYNTHESIS OF 1-ALKYL-2-ACETYL-SN-GLYCERO-3-PHOSPHATE BY MICROSOMAL ACETYLTRANSFERASE OF IMMATURE RABBIT CEREBRAL-CORTEX

The activity of 1-alkyl-sn-glycero-3-phosphate (AGP) acetyltransferase was studied using microsomal fractions isolated from cerebral cortices of 15-day-old rabbits. Fraction P(3)A was isolated using buffered 0.32 M sucrose containing mercaptoethanol, EDTA and NaF. This fraction had specific AGP acetyltransferase activities which were 4.9-times those of microsomal fraction P3B isolated in 0.32 M sucrose alone. This P3B activity was increased 2.4-times after a preincubation in the presence of ATP, MgCl2 and a high-speed supernatant fraction from cerebral cortex. Further, the activities of both P(3)A and P3B were almost completely eliminated by preincubation in the presence of alkaline phosphatase. Thus an activation of the AGP acetyltransferase by phosphorylation was indicated. While there was little inhibition of the P(3)A AGP acetyltransferase in the presence of added ATP, the magnesium salt form of ATP (1 mM) was severely inhibitory, bringing about 86% inhibition for P(3)A and 91% for P3B. The inhibitory effects of MgADP and MgAMP were smaller, and MgATP was a much more effective inhibitor than MgCTP, MgGTP and MgUTP which brought about 20-38% inhibitions of P(3)A activity at 1 mM concentrations. The effect of MgATP may be of particular relevance to the synthesis of platelet activating factor (PAF) following a period of ischemia in brain. Falling MgATP levels during energy failure could relieve the inhibition of AGP acetyltransferase seen in healthy cells and allow the formation of 1-alkyl-2-acetyl-sn-glycero-3-phosphate, which is the first committed intermediate in the de novo pathway of PAF synthesis.