An activation mechanism of platelet phospholipases
Prostaglandins and thromboxanes have been implicated with platelet function (see Samuelsson et al. 1978 for review). Since the converting enzyme in their synthesis is highly active in platelets, its efficiency is considered to be limited by the availability of substrate, arachidonate. Because of this, the release of arachidonate from phospholipids by phospholipases has been regarded as the rate limiting step in the synthesis of prostaglandins and thromboxanes. Many cells and tissues can release arachidonate in response to stimulation, and platelets serve as the most fitted experimental system for study of this phospholipase reaction. Since arachidonate is esterified almost exclusively at the sn-2-position of glycerol of phospholipids in platelets, it had been generally assumed that activation of the enzyme having an A2 specificity is responsible for the release of arachidonate. However, free arachidonate can be released not only by phospholipase A2 alone, but also by the combined action of either phospholipase A1 plus lysophospholipase, or phospholipase C plus DG and MG lipases. Plasmalogenases could also participate in the reaction. It has been rather difficult to elucidate the exact pathway of arachidonate release by studying arachidonate release from the endogenous phospholipid pool of intact platelets, and the detailed enzymological study to test these various possible pathways has not been started until recently.
KeywordsCholesterol Hydrolysis Prostaglandin Indomethacin Phosphatidylcholine
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