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Fatty Acyl‐CoA Inhibits 1‐Alkyl‐ sn ‐Glycero‐3‐Phosphate Acetyltransferase in Microsomes of Immature Rabbit Cerebral Cortex: Control of the First Committed Step in the De Novo Pathway of Platelet‐Activating Factor Synthesis
Author(s) -
Baker R. Roy,
Chang HuuYi
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64010364.x
Subject(s) - acetyltransferase , chemistry , acyltransferase , microsome , biochemistry , acyl coa , substrate (aquarium) , acetyl coa , enzyme , choline acetyltransferase , stereochemistry , acetylation , endocrinology , cholinergic , biology , gene , ecology
Microsomal fractions of cerebral cortices of 15‐day‐old rabbits were used to study the 1‐alkyl‐ sn ‐glycero‐3‐phosphate (AGP) acetyltransferase that generates 1‐alkyl‐2‐acetyl‐ sn ‐glycero‐3‐phosphate in the de novo path of platelet‐activating factor synthesis. The AGP acetyltransferase activity was inhibited by small concentrations of medium‐long chain fatty acyl‐CoA thioesters. In contrast, the AGP acyltransferase used oleoyl‐CoA as substrate and was not inhibited by the presence of acetyl‐CoA in high molar excess. The inhibition of AGP acetyltransferase was seen at concentrations of oleoyl‐CoA as low as 0.5 µ M using 12.5 µ M AGP and 200 µ M acetyl‐CoA. The inhibition by oleoyl‐CoA was noncompetitive for the acetyl‐CoA substrate. However, there was evidence that the oleoyl‐CoA was competing with AGP in the acetyltransferase reaction, as the inhibition was lessened by increasing the AGP substrate concentration. Several acyl‐CoA thioesters were effective as inhibitors of the AGP acetyltransferase, including oleoyl‐, palmitoyl‐, lauroyl‐, and octanoyl‐CoA. Propionyl‐ and butyryl‐CoA were less effective as inhibitors, and propionyl‐CoA was found to be a competitive inhibitor for acetyl‐CoA. We have noted earlier that MgATP is an effective inhibitor of the AGP acetyltransferase and here we show that the inhibition by oleoyl‐CoA can be increased by the presence of 0.1 m M MgATP. In brain ischemia, a decline in ATP levels would likely lead to a corresponding fall in acyl‐CoA concentrations, thereby relieving the inhibition of AGP acetyltransferase and permitting the flow of AGP into the de novo pathway of platelet‐activating factor synthesis.