Action of phospholipase A2 on bilayers containing lysophosphatidylcholine analogs and the effect of inhibitors.

The effects of several lysophospholipid analogs on the phase properties of codispersions with diacylphosphatidylcholine with or without fatty acids were examined. These ternary codispersions were readily hydrolyzed by phospholipase A2, and they underwent a rapid change in turbidity. Nonideal mixing or phase separation in the ternary codispersions is postulated to be responsible for their enhanced susceptibility to pig pancreatic phospholipase A2, as well as for their tendency to undergo spontaneous change in turbidity, presumably due to spontaneous fusion of the vesicles. Both of these processes were inhibited by a variety of structurally unrelated solutes like n-hexanol and mepacrine. These and other observations are interpreted to suggest that structural defects in bilayers of ternary codispersions are a common locus for the binding of phospholipase A2 and are responsible for the process underlying the change in turbidity. The experiments described here suggest that many of the common inhibitors of phospholipase A2 owe their effects to their ability to modify the quality of the substrate interface, rather than to a direct interaction with the enzyme.