Benesch Matthew G K, Lewis Ruthven N A H, Mannock David A, McElhaney Ronald N
Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Chem Phys Lipids. 2015 May;188:10-26. doi: 10.1016/j.chemphyslip.2015.03.002. Epub 2015 Mar 21.
We present the results of a comparative differential calorimetric and Fourier transform infrared spectroscopic study of the effect of cholesterol and five analogues on the thermotropic phase behaviour and organization of dipalmitoylphosphatidylcholine bilayer membranes. These sterols/steroids differ in both the nature and stereochemistry of the polar head group at C3 (β-OH, α-OH or CO) and in the presence or absence of a double bond in ring B and in the orientation of rings A and B. The Δ(5) sterols/steroid have a trans rather than a cis ring A/B junction, and the concentration of these compounds required to abolish the DPPC pretransition, inversely related to their relative ability to disorder gel state DPPC bilayers, decreases in the order β-OH > α-OH > CO. However, in the saturated ring junction-inverted (cis) series, these concentrations are much more similar, regardless of polar head group chemical structure. Similarly, the residual enthalpy of the DPPC main phase transition at 50 mol% sterol/steroid, which is inversely related to the miscibility of these compounds in fluid DPPC bilayers, also increases in the order β-OH > α-OH > CO, but this effect is attenuated in the saturated series with an inverted ring A/B orientation. Moreover, replacement of the double bond at C5-C6 with a saturated linkage and inversion of the ring A/B junction reduces both sterol/steroid solubility and the ability to order the hydrocarbon chains of fluid DPPC molecules all cases. Thus, the characteristic effects of sterols/steroids on fluid lipid bilayers are generally optimal when an OH group rather than CO group is present at C3, and when this OH group is in the equatorial (β) orientation, and when the orientation of the ring A/B fusion is trans rather than cis. Overall, these results demonstrate that variations in the saturation and stereochemistry of the steroid ring system influence the effect of variations in the nature and stereochemistry of the polar headgroup at C3 on the physical properties of phospholipid bilayers and vice versa. Moreover, the presence of a single double bond specifically at Δ(5) is required to maximize sterol solubility in fluid DPPC bilayers.
我们展示了一项比较性的差示量热法和傅里叶变换红外光谱研究结果，该研究旨在探究胆固醇及其五种类似物对二棕榈酰磷脂酰胆碱双层膜的热致相行为和结构的影响。这些甾醇/类固醇在C3处极性头基团的性质和立体化学（β-OH、α-OH或CO）、环B中双键的有无以及环A和环B的取向方面存在差异。Δ(5)甾醇/类固醇具有反式而非顺式的环A/B连接，消除DPPC预转变所需的这些化合物的浓度与其使凝胶态DPPC双层膜无序化的相对能力呈反比，其顺序为β-OH > α-OH > CO。然而，在饱和环连接倒置（顺式）系列中，无论极性头基团的化学结构如何，这些浓度更为相似。同样，在50 mol%甾醇/类固醇时DPPC主相变的残余焓，与这些化合物在流体DPPC双层膜中的混溶性呈反比，也按β-OH > α-OH > CO的顺序增加，但在具有倒置环A/B取向的饱和系列中这种效应会减弱。此外，在所有情况下，用饱和键取代C5 - C6处的双键以及环A/B连接的倒置都会降低甾醇/类固醇的溶解度以及使流体DPPC分子的烃链有序化的能力。因此，当C3处存在OH基团而非CO基团时，当该OH基团处于赤道（β）取向时，以及当环A/B融合的取向为反式而非顺式时，甾醇/类固醇对流体脂质双层膜的特征性影响通常最为显著。总体而言，这些结果表明，类固醇环系统的饱和度和立体化学变化会影响C3处极性头基团的性质和立体化学变化对磷脂双层膜物理性质的影响，反之亦然。此外，在Δ(5)处特异性存在单个双键是使甾醇在流体DPPC双层膜中溶解度最大化所必需的。
