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The control of prostaglandin and leukotriene biosynthesis in inflammatory and other cells depends on the enzymatic release of free arachidonic acid from the sn-2 position of membrane phospholipids. Although many types of phospholipases have been implicated, a phospholipase A2 is the simplest and most obvious candidate for the responsible enzyme. Studies on the phospholipase A2 from snake venom and mammalian pancreas provide a paridigm for the phospholipases responsible for arachidonic acid release. Additionally, they provide the best source of a readily available, pure, stable phospholipase to test potential inhibitors. Different kinds of inhibitors require different analytical strategies. Reversible inhibitors, including polycyclic aromatic dyes, fatty acids and amide ether analogues of phospholipids will be considered as well as irreversible inhibitors such as p-bromophenacyl-bromide and manoalide, an unusual natural product obtained from sponge and which may act by a novel mechanism. Protein inhibitors of the lipocortin type may inhibit by a “substrate depletion model”. Meaningful interpretation of inhibitor studies can only be accomplished within the framework of an understanding of the enzyme's kinetics and mechanism of action at the lipid-water interface. . © 1987 Nature Publishing Company
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