Arachidonate—Phospholipid Remodeling and Cell Proliferation

Abstract

It has been recognized since the mid-1980’s that arachidonic acid is taken up and remodeled between as many as 20 different glycerolipid molecular species in most cell types [1]. However, it has been difficult to understand why it is necessary for mammalian cells to maintain so many different arachidonate-containing glycerolipids and the ramifications of remodeling arachidonate between different glycerolipid molecular species. It is known that arachidonate-phospholipid remodeling occurs at a relative“slow” rate in most resting cells but this rate can be accelerated many fold during priming or stimulation of cells [2, 3]. Recently, we have begun to utilize newly-discovered inhibitors of the enzyme, CoA-independent transacylase (CoA-IT), which is thought to remodel arachidonate into the phospholipid subclass 1-alkyl-2-arachidonoyl-GPC and ethanolamine-containing phospholipids. Using these inhibitors of remodeling, it has been discovered that rapid remodeling of arachidonate is probably necessary to support continued arachidonic acid release and PAF generation which is initiated by phospholipase A₂.