title: Regulation of lipases by lipid-lipid interactions: implications for lipid-mediated signaling in cells.
abstract: Lipases are extracellular peripheral proteins that act at the surface of lipid emulsions stabilized, typically, by phospholipids. At a critical composition lipase activity toward substrates in phospholipid monolayers is discontinuously switched on by a small increase in substrate mole fraction. This occurs in part because lipase binding is inhibited by phospholipids. Binding of the lipase cofactor, colipase, is also inhibited by phospholipids. The initial rate of colipase binding increases abruptly at a substrate mole fraction that is approximately half the critical composition for lipase activity and just above that in substrate-phospholipid complexes. Moreover, complex collapse areas show an approximately 1:1 correlation with phospholipid excluded areas determined from an analysis of colipase adsorption rates. Thus, complexes inhibit colipase binding rate. Additionally, the switching of lipase activity likely occurs when uncomplexed substrate becomes the majority species in the interface. Lipase substrates, e.g. diacylglycerols, are typically the same lipids generated in the cytoplasmic surface of the plasma membrane of stimulated cells. As colipase binding is nonspecific and complexes involving lipase substrates form on the basis of lipid-lipid interactions alone, complexes should form in the plasma membrane of stimulated cells and may regulate protein translocation to the membrane.
authors.affiliation: Department of Biomathematical Science, Mt Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: I P
authors.initials: IP
authors.lastname: Sugar
authors.forename: N K
authors.initials: NK
authors.lastname: Mizuno
authors.forename: M M
authors.initials: MM
authors.lastname: Momsen
authors.forename: W E
authors.initials: WE
authors.lastname: Momsen
authors.forename: H L
authors.initials: HL
authors.lastname: Brockman
mesh_terms: D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D050356:Lipid Metabolism; D015398:Signal Transduction
chemical_list: D008049:Lipase