化学系-脂类代谢2.ppt

动脉粥样硬化 动脉内膜形成的胆固醇斑纹造成动脉的粥样硬化。患者血液[胆固醇]或[胆固醇]/磷脂升高，脂质向动脉内膜浸润而粘着于血管壁，形成动脉粥样斑。 过去认为是摄入过高胆固醇的缘故—膳食假说。但生物体内有90%以上的胆固醇是体内合成的（内源性的）。因此控制动脉粥样硬化应考虑胆固醇合成、分解及排泄速度等各方面的因素。 动脉粥样硬化斑 HMG-CoA还原酶抑制剂 * 680-682,683 * 人类 * 原核生物 * 703 * 694 * 695 * 701 * 701 * 701，COMPACTIN is another representative of a new class of cholesterol-lowering agents, the HMG-CoA reductase inhibitors. Though because of multiple side effects Compactin is not used as a medicine it is an important source for producing PRAVASTATIN (one of advanced cholesterol-lowering agents). ZOCOR is a prescription drug that is indicated as an addition to diet for many patients with high cholesterol when diet and exercise are inadequate. For patients with coronary heart disease (CHD) and high cholesterol, ZOCOR is indicated as an addition to diet to reduce the risk of death by reducing coronary death; to reduce the risk of heart attack; to reduce the risk for undergoing cardiac procedures (coronary artery bypass grafting and percutaneous transluminal coronary angioplasty); and to reduce the risk of stroke or transient ischemic attack (TIA). Pravastatin is a member of the HMG-CoA reductase inhibitor family of drugs, also called “statins,” such as lovastatin and simvastatin. Pravastatin blocks a key step in the body’s production of cholesterol and is used to lower cholesterol levels in people with hypercholesterolemia 甘油磷脂的酶解 磷脂酶的种类和作用 A1广泛存在于动物的细胞膜、线粒体膜上，Ca2+为其激活剂，专一水解磷脂分子C1上的酯键，水解产物为溶血磷脂2（lysophosphoglycerides-2)。 A2存在于动物组织溶酶体中，蛇毒、蝎毒、蜂毒等亦含有，专一水解C2上的酯键，产物为溶血磷脂1。 B为混合磷脂酶，水解A2水解产物1-脂酰磷脂C1上的酯键和A1水解产物2-脂酰磷脂C2上的酯键，是溶血磷脂酶。 C主要存在于动物脑、蛇毒和微生物中，作用于磷脂酸C3位的磷酸酯键。 D主要存在于高等植物，水解C3位第2个磷酸酯键。 膜磷脂合成(甘油磷脂) ????????????????????????????????????????????? PC, PE和PS的生物合成 肝 甲基[化]引入 进一步甲基化生成卵磷脂 CDP-二脂酰甘油 ??????????????????????????????????? PI，PG和心磷脂的生物合成 大肠杆菌磷脂极性头部的来源 甲基化 (S-腺苷甲硫氨酸) phosphatidylcholine 卵磷脂和磷脂酰乙醇胺合成途径总结 1.磷脂交换蛋白(Phospholipid exchang proteins) 2.二软脂酰胆碱 鞘磷脂和鞘糖脂的合成拥有相同的前体及一些相同的过程 鞘磷脂的生物合成包括四步反应： 1）由软脂酰-CoA和丝氨酸合成十八碳胺—二氢鞘氨醇； 2