Control of arachidonate levels within inflammatory cells

Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes

“…The Lands cycle is a mechanism for the deacylation/reacylation of membrane PLs by which polyunsaturated fatty acids, such as AA, are incorporated into different species (2)(3)(4). Although many studies have been conducted in resting cells, much less is known on the regulatory features of PL AA incorporation in activated cells, where the sustained activation of cPLA 2 a results in a rate of AA release that exceeds that of reacylation back into PLs.…”

“…AA is an intermediate of a deacylation/reacylation cycle of membrane phospholipids (PLs), the so called Lands cycle, in which AA liberated by phospholipase A 2 (PLA 2 ) is converted to arachidonoyl-CoA at the expense of ATP by arachidonoyl-CoA synthetases (ACSLs) and immediately incorporated into PL by CoA-dependent acyltransferases (2)(3)(4)(5). In resting cells, AA is predominantly found esterified in membrane PLs and is unavailable for eicosanoid biosynthesis.…”

“…Under stimulation conditions, the rate of AA release clearly exceeds that of reincorporation into PLs, hence net accumulation of AA occurs that is followed by its conversion into different eicosanoids. Despite that, in stimulated cells the AA deacylation reactions dominate, AA reacylation reactions are still very significant, as manifested by the fact that only a minor fraction of the free AA released by cPLA 2 a is converted into eicosanoids, the remainder being effectively incorporated back into PLs (2)(3)(4)(5). Once the AA has been incorporated into PLs, a remodeling process carried out by CoA-independent transacylase transfers AA from choline glycerophospholipids (PCs) to ethanolamine glycerophospholipids, in a process that takes several hours to take place in primary cells but is strikingly rapid in tumor cell lines (4,(20)(21)(22).…”

“…Depending on the concentration of free AA, there are two different pathways for the initial incorporation of this fatty acid into PLs, namely a low-capacity/high-affinity pathway and a highcapacity/low-affinity pathway (4). By means of the former, low concentrations of free AA incorporate into PLs via direct acylation of preexisting PLA 2 -derived lysophospholipids.…”

“…This pathway is believed to constitute the major pathway for AA incorporation into PLs in a variety of cells under physiological conditions; hence, the availability of lysophospholipid acceptors, particularly lysophosphatidylcholine (lysoPC), is a limiting factor (13,14,(23)(24)(25). The high-capacity/low-affinity pathway incorporates free AA via the de novo route, which ultimately results in the accumulation of AA into triacylglycerol and diarachidonoyl PLs (4,26). This latter pathway is thought to primarily function when the highaffinity deacylation/reacylation pathway has been saturated by exposure to high AA concentrations (4), which mostly occurs under pathological conditions.…”