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A transacylation reaction initiates PAF biosynthesis in the remodeling pathway

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:5312149
; ;  [1]
  1. Oak Ridge Associated Univ., TN (United States)
The remodeling pathway for the biosynthesis of platelet activating factor (PAF) consists of the following reaction sequence: alkylacyl-glycerophosphocholine (GPC) {endash}> lyso-PAF{endash}> PAF. In this investigation, the authors describe a novel transacylase activity that generates the lyso-PAF intermediate which can then be acetylated to form PAF. Alkyllysoglycerophosphoethanolamine (GPE), acyllyso-GPE, alk-1-enyllyso-GPE, unlabeled lyso-PAF, acyllyso-GPC and alk-1-enyllyso-GPC are all able to stimulate the formation of ({sup 3}H)lyso-PAF from a ({sup 3}H)alkylacyl-GPC precursor pool associated with HL-60 cell (granulocytic) membranes. Other glycerolipids with free hydroxyl groups, cholesterol, phosphatidylcholine, and phosphatidylethanolamine had no stimulatory effect on the release of ({sup 3}H)lyso-PAF from the prelabeled membranes under identical conditions. The transacylase responsible for the release of lyso-PAF from the membrane-associated alkylacyl-GPC is not affected by Ca{sup 2+}, EGTA, or a known phospholipase A{sub 2} inhibitor, p-bromophenacyl bromide. The observed transacylase reaction is directly coupled to PAF production since the addition of alk-1-enyllyso-GPE to HL-60 membranes in the presence of ({sup 14}C)acetyl-CoA stimulates PAF formation.
DOE Contract Number:
AC05-76OR00033
OSTI ID:
5312149
Report Number(s):
CONF-9104107--
Conference Information:
Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 5:4
Country of Publication:
United States
Language:
English