The Role of a COA-Independent Transacylase in the Movement of Arachidonate among Phospholipids and the Synthesis of PAF

Abstract

The metabolism of arachidonic acid is closely linked to the biosynthesis of platelet activating factor (PAF) and related O-alkyl- and O-alk-1-enyl-containing phospholipids. In this article, we describe several important factors (concentration of arachidonate, number of cells, cell differentiation, and time) that influence the movement of arachidonic acid among subclasses of acyl and ether-linked glycerolipids in HL-60 cells (undifferentiated and those differentiated into a granulocytic form). Kinetic studies in pulse- chase experiments indicate the final destination of arachidonate is the ethanolamine plasmalogens, which may be an important source for the release of 20:4 and PAF biosynthesis under certain conditions. In addition, our results also indicate differentiated HL-60 cells possess a novel CoA-independent transacylase that transfers 20:4 from alkylarachidonoyl-glycerophosphocholine to a lyso-phospholipid that serves as the acceptor molecule for the arachidonate. The resulting lyso-PAF is then acetylated to form PAF. The lyso-phospholipid acceptors (only choline- and ethanolamine-containing lyso- glycerophosphatides) for the transfer of the 20:4 group from the alkylarachidonoylgly- cerophosphocholne pool are believed to be generated in situ through the action of a putative phospholipase A2 activity.