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 P3A 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 P3A 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 P3A AGP acetyltransferase in the presence of added ATP, the magnesium salt form of ATP (1 mM) was severely inhibitory, bringing about 86% inhibition for P3A 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 P3A 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.
Department of Medicine, University of Toronto, Ontario, Canada.
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Baker
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Chang
D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D005994:Glycerophosphates / Q000096:biosynthesis*; D015636:Magnesium Chloride / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D011817:Rabbits; D013535:Suspensions
D005994:Glycerophosphates; D013535:Suspensions; D015636:Magnesium Chloride; D000255:Adenosine Triphosphate; D000123:Acetyltransferases; C052591:alkylglycerophosphate 2-O-acetyltransferase; D002122:Calcium Chloride