title: Lipid bilayer heterogeneities and modulation of phospholipase A2 activity.
abstract: The regulation of phospholipase A2 (PLA2) activity toward synthetic vesicular substrates is a model for the modulation c enzyme function by biological membranes. PLA2's catalytic rate toward membrane phospholipids can be modified by several order of magnitude by altering the membrane's composition and structure. The physical basis of this sensitivity is the subject of thi report. The results described here imply that the salient features of membrane-structure which modulate PLA2 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 PLA2 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.
authors.affiliation: Department of Biochemistry, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: W R
authors.initials: WR
authors.lastname: Burack
authors.forename: R L
authors.initials: RL
authors.lastname: Biltonen
mesh_terms: D004789:Enzyme Activation; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000494:pharmacology; D008566:Membranes / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2