Regulation Of The Fatty Acid Composition Of Platelet Phospholipids

Abstract

The fatty acid composition of cell membrane phospholipids does not remain constant after de novo biosynthesis, but undergoes continual remodelling. One of the major routes for remodelling probably includes the deacylation-reacylation steps of the Lands Pathway. This has been shown to be important for the incorporation of long chain, polyunsaturated fatty acids into phospholipids by liver and brain. An understanding of the mechanisms involved in these processes in platelets is especially important in light of the large stores of arachidonic acid (AA) in platelet phospholipids and the role of AA in hemostasis and thrombosis. Previous results from this laboratory have shown that the turnover of radioactive AA, 8,11,14-eicosatrienoic and 5,8,11,14,17-eicosapentaenoic acids in the phospholipids of resting platelets is more rapid than the turnover of radioactive C16 and C18 saturated and unsaturated fatty acids. However, little is known about how fatty acids, especially AA and its homologues, are incorporated into platelet phospholipids during de novo biosynthesis or how they are exchanged during remodelling.At least three enzymes are involved in the deacylation- reacylation of phospholipids: phospholipase A2; acyl CoA synthetase; and acyl CoA transferase. We have studied acyl CoA transferase and have found considerable activity in human platelet membranes. Experiments are in progress to determine the substrate specificity and other properties of this enzyme.