Alkylglycerophosphate acetyltransferase and lyso platelet activating factor acetyltransferase, two key enzymes in the synthesis of platelet activating factor, are found in neuronal nuclei isolated from cerebral cortex.
Neuronal nuclear fractions (N1) isolated from cerebral cortices of 15-day-old rabbits were enriched in two acetyltransferases involved in biosynthetic pathways leading to platelet activating factor (PAF). Alkylglycerophosphate (AGP) acetyltransferase of the de novo biosynthetic path had specific activities in fraction N1 which were 3-times those of the microsomal fraction (P3D) from cerebral cortex. Lyso PAF acetyltransferase of the remodelling path had specific activities in N1 which were 16-times those of P3D and 51-times those of the homogenate. The maximum specific activity observed for the N1 AGP acetyltransferase was 1.4-times the corresponding N1 lyso PAF acetyltransferase value. The pH optimum for the N1 AGP acetyltransferase was within the alkaline range (pH 8-9), while the N1 lyso PAF acetyltransferase showed a much broader pH optimal range which extended over the neutral and physiological pH values. Both acetyltransferases were inhibited by MgATP (0.125-1 mM) or oleoyl CoA (2-10 microM). However, the N1 AGP acetyltransferase could be distinguished from the N1 lyso PAF acetyltransferase by a greater sensitivity to MgATP inhibition. When NaF was not present in the assays, less of the product of N1 AGP acetyltransferase was recovered, likely indicating a hydrolysis of the acetylated AGP. When the AGP and lyso PAF substrates were combined in acetyltransferase assays, the two N1 acetylations appeared to proceed independently. The enrichment of the acetyltransferases, and particularly the lyso PAF acetyltransferase, within the neuronal nuclear fraction is of particular interest with respect to the intracellular effects of PAF which are considered to be involved in nuclear signalling mechanisms.
Baker
R R
RR
Department of Medicine, University of Toronto, Ontario, Canada.
Chang
H Y
HY
D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology / Q000648:ultrastructure*; D006863:Hydrogen-Ion Concentration; D009474:Neurons / Q000201:enzymology / Q000648:ultrastructure*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D011817:Rabbits
D000214:Acyl Coenzyme A; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; C017585:oleoyl-coenzyme A; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase