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.
