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

The regulation of phospholipase A(2) (PLA(2)) activity toward syntheti c vesicular substrates is a model for the modulation of enzyme functio n by biological membranes. PLA(2)'s catalytic rate toward membrane pho spholipids can be modified by several orders of magnitude by altering the membrane's composition and structure. The physical basis of this s ensitivity is the subject of this report. The results described here i mply that the salient features of membrane-structure which modulate PL A(2) activity include: compositional phase separation; membrane curvat ure and, possibly, curvature-associated defects; and dynamic product i nhibition 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 en hancing association of PLA(2) with the membrane surface: a membrane-bo und inactive state is spectroscopically identified. Finally, these res ults are discussed in the context of some published models for the rol e of membrane structure in the regulation of membrane-bound enzymes.