Lipolysis of phospholipids in model cholesteryl ester rich lipoproteins and related systems: effect of core and surface lipid phase state.
Lipolysis of phospholipids in model cholesteryl ester rich lipoproteins and related systems: effect of core and surface lipid phase state.
复制标题
富含胆固醇酯的脂蛋白模型和相关系统中磷脂的脂解：核心和表面脂质相状态的影响。
DOI：
10.1021/bi00414a051
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发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
Morrisett,JD
中科院分区：
文献类型：
--
作者：
Mims,MP;Morrisett,JD
Departments of Medicine and Biochemistry, Baylor College of Medicine and The Methodist Hospital, Houston, Texas 77030 Received January 4, 1988; Revised Manuscript Received March 28, 1988 abstract: Porcine pancreatic phospholipase A2 (PL A2) was used as a probe to study the structure of phospholipid domains of dimyristoylphosphatidylcholine (DMPC) vesicles ą 2% cholesteryl oleate (CO), of discoidal structures formed by the interaction of apolipoprotein E (apoE) with these vesicles, and of large CO/DMPC microemulsion particles ą apoE. Results of phospholipid hydrolysis over a range of temperatures were compared with the thermal transitions of the lipid components of the particles as measured by differential scanning calorimetry. These studies revealed that DMPC vesicles were most susceptible to digestion at or near the transition temperature. A similar result was obtained with DMPC/apoE disks; however, these particles were hydrolyzed over a broader temperature range than the vesicles. DMPC/CO vesicles were resistant to hydrolysis at every temperature tested; however, discoidal structures formed by interaction of apoE with these vesicles were hydrolyzed maximally above their thermal transition. Large microemulsion particles of CO and DMPC were poor substrates for the enzyme at every temperature; binding of apoE to these particles improved the ability of PL A2 to hydrolyze the phospholipid. These results suggest that the curvature of the surface, the presence of dissolved cholesteryl ester, and the binding of protein have profound effects on the temperature and breadth of the phospholipid phase transition and on the accessibility of the phospholipid to hydrolysis by PL A2. e mobility and structure of phospholipid domains in a variety of particle types havebeen examinedby several physical techniques including NMR, EPR, and fluorescence spec-troscopy (Sklar et al., 1977; Pownall et al., 1978; Barrett et al., 1969; Hubbell & McConnell, 1971; Brainard et al., 1984; Novosad et al., 1976; Krieger et al., 1980). These studies have provided useful information about the dynamics of phospho-lipid motion in vesicles, protein/phospholipid disks, lipoproteins, and microemulsion particles. However, the acces-sibility and reactivity of phospholipid molecules in various domains have not been examined and systematically compared. In the past, pancreatic phospholipase A2, which is very sensitive to the structure of the phospholipid/water interface, has been used to determine the accessibility of phospholipid invesicles and liposomes (Wilschut et al., 1979a, b; Goormaghtigh et al., 1981; de Haas et al., 1968). Unlike the snake venom phospholipases which are able to hydrolyze phospholipids in a wide variety of substrate particles, pancreatic phospholipase A2 (PL A2)'has strict substrate requirements in terms of the physical form of the phospholipid. Wilschut et al.(1979) have shown that the pancreatic enzyme will hydrolyze dimyristoyl-phosphatidylcholine (DMPC) liposomes only in the temper-ature region surrounding the gel—liquid-crystalline phase transition (15-26 C). Hydrolysis of small, unilamellar DMPC vesicles occursover a slightly larger temperaturerange; these particles are better substrates presumably because their highly curvedsurfaces induce defects in lipid packing which facilitate penetration of the lipase. Op den Kamp et al.(1975) f This work has been supported by a Specialized Center of Research in Atherosclerosis (HL-27341) and by a grant from the Robert A. Welch Foundation (Q-837). MPM is the recipient of a National Research Service award (HL-07341) from the National Heart, Lung, and Blood Institute.
