METABOLIC AND STRUCTURAL STUDIES OF POLYUNSATURATED LIPIDS IN CELL MEMBRANES

细胞膜中多不饱和脂质的代谢和结构研究

• 批准号: 4687722
• 负责人: N SALEM
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4687722
• 关键词: brain metabolism; chemical structure function; ethanol; fatty acid biosynthesis; fatty acid metabolism; high performance liquid chromatography; human tissue; leukotrienes; lipid structure; mass spectrometry; membrane lipids; membrane structure; phospholipids; unsaturated fatty acids

The principal objectives of this study are to elucidate the structural and metabolic functions of polyunsaturated fatty acids or phospholipids with particular reference to their modulation by ethanol. To this end, we investigated novel routes and sources of oxygenated metabolites of the major polyunsaturate of the brain, docosahexaenoic acid (22:6). Chromatographic, mass spectrometric, and extraction techniques were developed in order to characterize C22:6 products enzymatically formed by rat brain homogenate in vitro. We observed several mono-, di-, and trihydroxylated products which have not been previously described. These structural identifications were obtained after HPLC-thermospray MS in the positive ion mode and negative ion thermospray analysis of the pentafluorobenzyl derivatives of purified peaks. In combination with organic reactions such as hydrogenation and methoximation, trihydroxy-22:6 and -22:5, dihydroxy-22:5, and monohydroxy-22:6 peaks were assigned. The synthesis of these leukotriene-like products is stimulated by low concentrations of ethanol. Progress in analyzing the structural functions of unsaturated lipids was made by the development of rapid and efficient phospholipid molecular species analysis by HPLC-thermospray. Simple and information-rich fragmentation patterns, which readily yield head group and fatty acyl composition, were observed. This analytic technique has been successfully applied to complex biological mixtures for choline, ethanolamine, and serine phosphoglycerides.

这项研究的主要目标是阐明结构和 多不饱和脂肪酸或磷脂的代谢功能 特别提到乙醇对它们的调节作用。为此，我们 研究了含氧代谢产物的新途径和来源 大脑的主要多不饱和物，二十二碳六烯酸(22：6)。 层析、质谱分析和提取技术 开发用于表征C22：6产物的酶促形成 大鼠脑匀浆体外培养。我们观察到了几个单声道、双声道和 以前没有描述过的三羟基化产物。这些 经高效液相色谱-热喷雾电喷雾联用鉴定 正离子模式和负离子热喷雾分析 纯化峰的五氟苯基衍生物。结合使用 三羟基-22：6的氢化和甲氧肟化等有机反应 和-22：5、二羟基-22：5和单羟基-22：6峰被指认。这个 低氧刺激这些类白三烯产物的合成 乙醇的浓度。 不饱和脂类的结构功能研究进展 由开发快速高效的磷脂分子制成 高效液相色谱-热喷雾法进行物种分析。简单而信息丰富 碎裂模式，容易产生头基和脂肪酰基 成分进行了观察。这种分析技术已经成功地应用于 适用于胆碱、乙醇胺和 丝氨酸磷酸甘油酯。