Surface pressure-dependent cross-modulation of sphingomyelinase and phospholipase A2 in monolayers

We investigated the ways in which phospholipase A(2) and sphingomyelinase are mutually modulated at lipid interfaces. The activity of one enzyme is affected by its own reaction products and by substrates and products of the other enzyme; all this depends differently on the lateral surface pressure. Ceramide inhibits both the sphingomyelinase activity rate and the extent of degradation, and decreases the lag time at all surface pressures. Dilauroyl- and dipalmitoylphosphatidylcholine, the substrates of phospholipase A(2) (PLA(2)), do not affect sphingomyelinase activity. The products of PLA(2), palmitic acid and lysopalmitoylphosphatidylcholine, strongly enhance and shirt to high surface pressures the activity optimum and the cutoff point of sphingomyelinase. Palmitic acid also shifts to high surface pressures the cut-off point of PLA(2) activity. Sphingomyelin strongly inhibits PLA(2) at surface pressures above 5 mN/m, while ceramide shifts the cut-off point and the activity optimum to high surface pressures. The sphingolipids increase the lag time of PLA(2) at low surface pressures. Both phosphohydrolytic pathways involve different levels of control on precatalytic steps and on the rate of activity that appear independent on specific alterations of molecular packing and surface potential. The mutual lipid-mediated interfacial modulation between both phosphohydrolytic pathways indicates that phospholipid degradation may be self-amplified or dampened depending on subtle changes of surface pressure and composition.