MUTUAL MODULATION OF SPHINGOMYELINASE AND PHOSPHOLIPASE A(2) ACTIVITIES AGAINST MIXED LIPID MONOLAYERS BY THEIR LIPID INTERMEDIATES AND GLYCOSPHINGOLIPIDS

Sphingomyelinase activity against pure sphingomyelin monolayers is con stant up to a surface pressure of 18 mN/m and falls above it. Sphingom yelinase- and phospholipase A(2)-mediated phosphohydrolytic pathways a re mutually modulated by the presence of their respective substrates a nd products. At 15 mN/m non-substrate lipids such as ceramide at a mol e fraction of 0.1 in mixed films with the pure substrate, inhibit the sphingomyelinase activity. Ganglioside GM1, another ceramide-containin g complex sphingolipid, also inhibits sphingomyelinase activity, while a chemically related glycosphingolipid such as asialo-GM1 has no effe ct. The activity is unaltered by dipalmitoylphosphatidylcholine and by an equimolar mixture of its products of hydrolysis by phospholipase A (2), fatty acid and lysoderivative, but it is inhibited by only one of them or by dilauroylphosphatidylcholine. Phospholipase A(2) is inhibi ted by sphingomyelin, and activated by ceramide and by palmitic acid, one of the products of its own phosphohydrolytic reaction.