Institute of Science and Engineering, Kanazawa University, Kanazawa920-1192, Ishikawa, Japan.
Department of Lipid Life Science, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo162-8655, Japan.
J Phys Chem B. 2022 Nov 17;126(45):9316-9324. doi: 10.1021/acs.jpcb.2c06189. Epub 2022 Nov 5.
Ultra-long-chain fatty acids (ULCFAs) are biosynthesized in certain types of tissues, but their biological roles remain unknown. Here, we report how the conformation of ULCFAs depends on the length and unsaturated-bond ratio of the ultra-long chains and the composition of the host bilayer membrane using molecular dynamics simulations. The ultra-long chain of ULCFAs flips between the two leaflets and fluctuates among three conformations: elongated, L-shaped, and turned. Furthermore, we found that the saturated ultra-long chain exhibited an elongated conformation more frequently than the unsaturated chain. In addition, the truncation of the ultra-long chain at C26 had little effect on the remaining ULCFAs. ULCFAs respond to lipid-density differences in the two leaflets, and the ratio of the elongated and turned conformations changed to reduce this difference. However, in cholesterol-containing membranes, ULCFAs exhibit no density difference after the flip-flop of cholesterol removes the difference.
超长链脂肪酸 (ULCFA) 在某些类型的组织中合成，但它们的生物学作用尚不清楚。在这里，我们使用分子动力学模拟报告了 ULCFA 的构象如何取决于超长链的长度和不饱和键比例以及主体双层膜的组成。超长链脂肪酸的超长链在两个叶层之间翻转，并在三种构象之间波动：伸长、L 形和翻转。此外，我们发现饱和超长链比不饱和链更频繁地表现出伸长构象。此外，超长链在 C26 处的截断对剩余的 ULCFA 几乎没有影响。ULCFA 对双层膜中脂质密度差异做出反应，并且伸长和翻转构象的比例发生变化以减小这种差异。然而，在含有胆固醇的膜中，胆固醇的翻转消除了差异后，ULCFA 不再表现出密度差异。
