Action of phospholipase A2 on bilayers. Effect of fatty acid and lysophospholipid additives on the kinetic parameters

Changes in a Phospholipid Bilayer Induced by the Hydrolysis of a Phospholipase A2 Enzyme: A Molecular Dynamics Simulation Study

“…Loss of integrity would also most likely appear in a partly hydrolyzed membrane. This is in accordance with the observations that, in addition to the presence of the hydrolysis products, varying perturbations may also activate PLA 2 by allowing more mobility of the substrate molecules in the membrane-normal direction and, accordingly, better access to the active site of the enzyme (Apitz-Castro et al, 1982;Jain and de Haas, 1983;Jain and Jahagirdar, 1985;Burack et al, 1993Burack et al, , 1995Burack et al, , 1997Sheffield et al, 1995;Lehtonen and Kinnunen, 1995;Bell et al, 1996;Hønger et al, 1996;Henshaw et al, 1998;Grandbois et al, 1998). In addition, the surface defects have been suggested to help interdigitation of the enzyme residues to the membrane and facilitate better contact between the membrane and the enzyme (Zhou and Schulten, 1996).…”

“…Interestingly, not only the accumulation of reaction products (Apitz-Castro et al, 1982;Burack et al, 1993Burack et al, , 1995Burack et al, , 1997Sheffield et al, 1995;Bell et al, 1996;Henshaw et al, 1998), but also several manipulations of zwitterionic bilayers are known to enhance the catalytic rate of PLA 2 . These manipulations include a change to the main phase transition temperature of the substrate (Jain and Jahagirdar, 1985;Bell et al, 1996;Hønger et al, 1996), osmotic stress (Lehtonen and Kinnunen, 1995), incorporation of diacylglycerol (Bell et al, 1996) or lyso-PC (Jain and de Haas, 1983), and perturbation with the atomic force microscope tip (Grandbois et al, 1998). The manipulations that activate PLA 2 appear to operate via different mechanisms and cause various perturbations in the bilayer.…”

“…The positively charged type II PLA 2 is known to interact preferentially with negatively charged membrane surfaces (Volwerk et al, 1986;Ghomashchi et al, 1991;Scott and Sigler, 1994;Han et al, 1997). In addition, various surface defects or perturbations caused, for example, by lipid peroxidation (McLean et al, 1993), by a change to the main phase transition temperature of the substrate (Jain and Jahagirdar, 1985;Bell et al, 1996;Hønger et al, 1996), by osmotic stress (Lehtonen and Kin-nunen, 1995), by incorporation of diacylglycerol (Bell et al, 1996) or lysophospholipids (Jain and de Haas, 1983), or even by pressure from the tip of the atomic force microscope (Grandbois et al, 1998) are known to activate PLA 2 .…”

Effects of Cholesterol on Physical Properties of Human Erythrocyte Membranes: Impact on Susceptibility to Hydrolysis by Secretory Phospholipase A2

“…Several previous studies have addressed relationships between sPLA 2 activity and the physical properties of artificial membranes (6)(7)(8)(9)(12)(13)(14)(15)(58)(59)(60)(61)(62). These relationships can be segregated into two categories.…”

“…The other category comprises specific perturbations to membrane structure that improve interactions of sPLA 2 with the membrane surface and/ or access of bilayer substrate to the enzyme's active site. Examples of these perturbations include increased surface curvature, negative surface charge, and the presence of bilayer contaminants that weaken phospholipid/neighbor interactions in the membrane (6)(7)(8)(9)(10)(12)(13)(14)(58)(59)(60). Even though these two categories are not entirely independent in terms of their mutual effects on membrane behavior and hydrolytic activity, we have classified them in this way because they appear to modulate the enzyme by separate means (7,8,14,64).…”