Key Lab of Bioorganic Phosphorous Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
J Phys Chem B. 2009 Dec 31;113(52):16537-46. doi: 10.1021/jp9074306.
Structural and kinetic properties of vitamin E in biomembranes provide the key to understanding the biological functions of this lipophilic vitamin. We report a series of molecular dynamics simulations of two alpha-tocopherol/phosphatidylcholine systems and two alpha-tocopherol/phosphatidylethanolamine systems in water at 280, 310, and 350 K. The preferential position, hydrogen bonding, orientation, and dynamic properties of the alpha-tocopherol molecule in the bilayers have been examined. In all the four systems simulated, the vitamin remains in one leaflet of lipid bilayer at 280 and 310 K but flips over from one side to the other at 350 K within 200 ns of the simulation. The hydroxyl oxygen in the headgroup of alpha-tocopherol preferred a location between the third and the fifth carbon atom in the sn-2 acyl chains of the lipids. Hydrogen bonding analysis shows that the hydrogen bonds are mainly with the oxygens of the fatty acid esters rather than with the phosphate oxygens of the lipid molecule, and those with the amino groups are trivial in the case of phosphatidylethanolamines, at all three temperatures. The hydrogen bonds with phosphatidylethanolamines are more stable than those with phosphatidylcholines at low temperatures. The orientation of alpha-tocopherol in the bilayers is relatively flexible: the chromanol ring takes various tilt angles with respect to the bilayer normal, and the isoprenyl chain is mobile and able to adopt many different conformers. Calculation of lateral diffusion coefficients of alpha-tocopherol and phospholipid molecules shows that alpha-tocopherol has a comparable diffusion rate with phospholipid molecules at the gel phase but diffuses more rapidly than lipid molecules at the liquid-crystal phase.
生物膜中维生素 E 的结构和动力学特性为理解这种亲脂性维生素的生物学功能提供了关键。我们报告了一系列在 280、310 和 350 K 下两种 α-生育酚/磷脂酰胆碱体系和两种 α-生育酚/磷脂酰乙醇胺体系的分子动力学模拟。研究了双层中 α-生育酚分子的优先位置、氢键、取向和动态特性。在所模拟的四个体系中，维生素在 280 和 310 K 时仍保留在脂质双层的一个叶层中，但在 350 K 时在 200 ns 内从一侧翻转到另一侧。α-生育酚头部基团中的羟基氧优先位于脂质 sn-2 酰基链的第三个和第五个碳原子之间。氢键分析表明，氢键主要与脂肪酸酯的氧而不是与脂质分子的磷酸氧形成，并且在三种温度下与磷脂酰乙醇胺的氨基形成的氢键微不足道。在低温下，与磷脂酰乙醇胺的氢键比与磷脂酰胆碱的氢键更稳定。双层中 α-生育酚的取向相对灵活：色满环相对于双层法线采取各种倾斜角度，异戊烯基链是可移动的，能够采用许多不同的构象。α-生育酚和磷脂分子的侧向扩散系数的计算表明，α-生育酚在凝胶相下与磷脂分子具有相当的扩散速率，但在液晶相下比脂质分子扩散得更快。
