培训课件-《生物技术药物》之重组多肽蛋白质类激素药物.ppt

黄体生成激素 luteinizing hormone (LH) alpha 亚基92个 氨基酸和beta 亚基120个氨基酸 绒毛膜促性腺激素 chorionic gonadotropins The α (alpha) subunit is 92 amino acids long. The β-subunit of hCG gonadotropin contains 145 amino acids * 各论五 重组多肽、蛋白质类激素药物 激素(hormone) 由腺体合成和释放，通过循环系统，作用于靶细胞周倜的微量化学信号分子。 特点：内分泌信号调节系统，作用远距离靶细胞。 包括两类：含氮激素和甾体激素。 含氮激素：胰岛素、胰高血糖素、生长素、促性腺激素等。 受体类型： 胰腺 B细胞(70%) A细胞(20%) D细胞(10%) 重组胰岛素 胰岛素(insulin) 胰岛素是含有51个氨基酸的小分子蛋白质，分子量为6000，胰岛素分子有靠两个二硫键结合的A链（21个氨基酸）与B链（30个氨基酸），如果二硫键被打开则失去活性。B细胞先合成一个大分子的前胰岛素原(109个氨基酸)，以后加工(-23个氨基酸)成八十六肽的胰岛素原，在细胞内的高尔基体中胰岛素原经水解(-2氨基酸)成为胰岛素(21+30)与连接肽(C肽33个氨基酸)。 胰岛素与C肽共同释入血中，也有少量的胰岛素原进入血液，但其生物活性只有胰岛素的3%-5%，而C肽无胰岛素活性。由于C肽是在胰岛素合成过程产生的，其数量与胰岛素的分泌量有平行关系，因此测定血中C肽含量可反映B细胞的分泌功能。 Beta cells in the islets of Langerhans release insulin in two phases. The first phase release is rapidly triggered in response to increased blood glucose levels. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar. The description of first phase release is as follows: Glucose enters the β-cells through the glucose transporter, GLUT2. Glucose goes into glycolysis and the respiratory cycle, where multiple, high-energy ATP molecules are produced by oxidation, leading to a rise in the ATP:ADP ratio within the cell. An increased intracellular ATP:ADP ratio closes the ATP-sensitive SUR1/Kir6.2 potassium channel (see sulfonylurea receptor). This prevents potassium ions (K+) from leaving the cell by facilitated diffusion, leading to a build up of potassium ions. As a result, the inside of the cell becomes more positive with respect to the outside, leading to the depolarisation of the cell surface membrane. On depolarisation, voltage-gated calcium ion (Ca2+) channels open which allows calcium ions to move into the cells by facilitated diffusion. An increased intracellular calcium ion concentration causes the activation of phospholipase C, which cleaves the membrane phospholipid phosphatidyl inositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate a