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首页> 外文期刊>Biochemistry >Spread monomolecular films of monohydroxy bile acids and their salts: influence of hydroxyl position, bulk pH, and association with phosphatidylcholine.
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Spread monomolecular films of monohydroxy bile acids and their salts: influence of hydroxyl position, bulk pH, and association with phosphatidylcholine.

机译:单羟基胆汁酸及其盐的单分子膜的扩散:羟基位置,整体pH值以及与磷脂酰胆碱的缔合的影响。

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摘要

Undissociated dihydroxy bile acids, alone or with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), lie with their long axes parallel to aqueous-lipid interfaces [Fahey, D. A., Carey, M. C., and Donovan, J. M. (1995) Biochemistry 34, 10886-10897]. To test the generality of this orientation, we used an automated Langmuir-Pockels surface balance to examine pressure-molecular area isotherms and dipole moments of insoluble monohydroxy bile acids and their salts, which are sparingly soluble because of their presumed high Krafft points. We studied lithocholic acid (LCA) (the natural 3alpha-OH isomer), glycolithocholic acid (GLCA) (its glycine conjugate), and the semisynthetic isomers, 7alpha-OH- and 12alpha-OH-cholanoic acids with and without POPC, at pH values ranging from 2 to 12. Monolayer collapse pressures increased sigmoidally with ionization, giving apparent pK values of 7.0-8.5 and implying a stronger affinity of the bile salt anions for the interface. At monolayer collapse, the molecular area of LCA was approximately 85 A(2) independent of pH, consistent with the steroid nucleus lying flat. In contrast, the interfacial area of 7-OH-cholanoic acid decreased from approximately 80 A(2) at pH 2 to approximately 40 A(2) above pH 9, consistent with a more vertical orientation and approximating 12-OH-cholanoic acid, which exhibited a molecular area of approximately 45 A(2) at all pH values. All monohydroxy bile acids condensed POPC monolayers more effectively at low than at high (ionized) pH. We conclude that the 3-OH group is crucial for anchoring bile acids and their salts to the aqueous interface, with all monohydroxy species condensing phospholipid membranes regardless of ionization state.
机译:未解离的二羟基胆汁酸,单独或与1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱(POPC)结合时,其长轴平行于水-脂质界面[Fahey,DA,Carey,MC和Donovan, JM(1995)Biochemistry 34,10886-10897]。为了测试该方向的一般性,我们使用了自动的Langmuir-Pockels表面平衡来检查不溶性单羟基胆汁酸及其盐的压力-分子面积等温线和偶极矩,由于假定的高Krafft点,它们难溶。我们研究了在pH值条件下的石胆酸(LCA)(天然的3alpha-OH异构体),巯基乙醇酸(GLCA)(其甘氨酸共轭物)以及半合成异构体,有和没有POPC的7alpha-OH-和12alpha-OH-胆酸值在2到12之间。随着电离作用,单层塌陷压力呈S形增加,表观pK值为7.0-8.5,这表明胆盐阴离子对界面的亲和力更强。在单分子层塌陷时,LCA的分子面积约为85 A(2),与pH值无关,与类固醇核平躺一致。相反,7-OH-胆酸的界面面积从pH 2时的大约80 A(2)降低到pH 9之上的大约40 A(2),这与更垂直的方向和大约12-OH-胆酸一致,在所有pH值下均显示出约45 A(2)的分子面积。与在高(电离)pH下相比,所有单羟基胆汁酸在低浓度下都能更有效地冷凝POPC单层。我们得出结论,3-OH基团对于将胆汁酸及其盐锚定到水界面至关重要,所有单羟基物质都会冷凝磷脂膜,而与电离状态无关。

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