LIPID BILAYER HETEROGENEITIES AND MODULATION OF PHOSPHOLIPASE A(2) ACTIVITY

The regulation of phospholipase A(2) (PLA(2)) activity toward synthetic vesicular substrates is a model for the modulation of enzyme function by biological membranes. PLA(2)'s catalytic rate toward membrane phospholipids can be modified by several orders of magnitude by altering the membrane's composition and structure. The physical basis of this sensitivity is the subject of this report. The results described here imply that the salient features of membrane-structure which modulate PLA(2) activity include: compositional phase separation; membrane curvature and, possibly, curvature-associated defects; and dynamic product inhibition due to limitations imposed by the rate of lateral diffusion of lipid in the membrane. Furthermore, it is shown that the effects of membrane structure on the catalytic rate are not exerted merely by enhancing association of PLA(2) with the membrane surface: a membrane-bound inactive state is spectroscopically identified. Finally, these results are discussed in the context of some published models for the role of membrane structure in the regulation of membrane-bound enzymes.