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Effect of Hydroperoxy Fatty Acids on Acylation and Deacylation of Arachidonoyl Groups in Synaptic Phospholipids
Author(s) -
Zaleska Malgorzata M.,
Wilson David F.
Publication year - 1992
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 - 10.1111/j.1471-4159.1992.tb09284.x
Subject(s) - chemistry , fatty acid , phosphatidylcholine , acylation , biochemistry , microsome , arachidonic acid , substrate (aquarium) , hydrolysis , phospholipid , phosphatidylinositol , synaptosome , in vitro , enzyme , membrane , biology , ecology , catalysis , kinase
The effect of hydroperoxy fatty acids on reactions involved in the acylation‐deacylation cycle of synaptic phospholipids was studied in vitro, using nerve ending fraction isolated from rat forebrain. 15‐Hydroperoxyeicosatetraenoic acid (15‐HPETE), 13‐hydroperoxylinoleic acid (13‐HP 18: 2), and hydroperoxydocosahexaenoic acid (22:6 Hpx), at 25 μ M final concentration, all inhibited the incorporation of [1‐ 14 C]arachidonate into synaptosomal phosphatidylinositol (PI), phosphatidylcholine (PC), and triacylglycerides by 50–80%. The lowest effective concentration of 15‐HPETE and 13‐HP 18:2 resulting in significant inhibition of the reacylation of PI was 5 μ M , whereas the inhibition of [1‐ 14 C]arachidonate incorporation into PC required 10 and 5 μ M hydroperoxy fatty acids, respectively. Cumene hydroperoxide and tert ‐butyl hydroperoxide at concentrations of 100 μ M did not inhibit reacylation of PI and PC. Synthesis of labeled arachidonoyl‐CoA from [1‐ 14 C]arachidonate was decreased by about 50% by 25 μ M hydroperoxy fatty acids both in synaptosomes and in the microsomal fraction. Use of [1‐ 14 C]arachidonoyl‐CoA as a substrate, to bypass the fatty acid activation reaction, revealed that activity of acyltransferase was not affected significantly by 25 μ M 15‐HPETE and 13‐HP 18:2. At the same time, however, the hydrolysis of labeled arachidonoyl‐CoA was substantially enhanced. Exposure of synaptosomes to 25 μ M fatty acid hydroperoxides did not affect significantly the endogenous concentrations of five major free fatty acids. It is concluded that (1) among synaptic phospholipids, reacylation of PI and PC is the most susceptible to the inhibitory action of fatty acid hydroperoxides, and (2) the enzymes affected by these compounds in nerve endings are arachidonoyl‐CoA synthetase and hydrolase.