ENCEPHALIN BIOSYNTHESIS IN ADRENAL MEDULLA

肾上腺髓质中的脑磷脂生物合成

• 批准号: 3072561
• 负责人: IRIS LINDBERG
• 金额: $ 4.57万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3072561
• 关键词: adrenal medulla; chromaffin cells; cow; enkephalins; enzyme mechanism; enzyme structure; genetic regulation; peptidases; protein biosynthesis; serine

The production of enkephalins, like the biosynthesis of other hormones, involves a sequential series of enzymatic steps culminating in the liberation of the active opioid sequences. Opioid peptides have been implicated in physiological processes ranging from blood pressure control to immunological function; the biochemical basis for the addictive properties of drugs may also relate to deficiencies in endogeneous levels or in the turnover of opioid peptides. It is therefore important to gain a good understanding of the biochemical mechanisms involved in opioid peptide biosynthesis. My short-term goals are to define the sequence of cleavages of proenkephalin as well as to investigate the presence of posttranslational modifications. Other short-term goals relate to the study of a putative proenkephalin processing enzyme, a serine protease present in chromaffin granules. My long- term objectives are to understand how biologically active peptides are synthesized. Ultimately I would like to be able to study the cellular regulation of proenkephalin processing, and to use molecular biological techniques to investigate general questions relating to the specificity of hormone processing proteases. The RCDA, if awarded, will assist me in accomplishing the goals outlined above in two ways. Firstly, it will free me from Departmental obligations such as substantial teaching in service courses, enabling me to devote my complete attention to research throughout the year. Secondly, by securing this award, I will be exempted from service on additional committees, both at a Departmental and Institutional level. The Department of Biochemistry and Molecular Biology provides a supportive environment for the development of my research career. The newly-established peptide synthesis/sequencing facility will enable on-site synthesis of peptides required for the above studies. Resource personnel able to provide direction in the techniques of molecular cloning are also present. The fact that Department faculty receive considerable support from federal granting agencies means that expertise and equipment is readily available through active research programs in surrounding laboratories. In short, the environment at L.S.U. provides an extremely favorable milieu in which to carry out the studies described in this proposal. The award of an RCDA will greatly speed the rate at which these studies are accomplished.

脑啡肽的产生，就像其他物质的生物合成一样 激素，涉及一系列连续的酶促步骤 最终释放出活性阿片样物质序列。 阿片肽与生理过程有关 从血压控制到免疫功能；这 药物成瘾特性的生化基础也可能 与内生水平或周转率的缺陷有关 阿片肽。 因此，获得良好的成绩非常重要 了解阿片类药物的生化机制 肽生物合成。 我的短期目标是定义 脑啡肽原的裂解序列以及研究 翻译后修饰的存在。 其他短期 目标与假定的脑啡肽原加工研究有关 酶，一种存在于嗜铬颗粒中的丝氨酸蛋白酶。 我的长- 术语目标是了解生物活性肽如何 被合成。 最终我希望能够 研究脑啡肽原加工的细胞调节，以及 使用分子生物学技术来研究一般 与激素加工的特异性相关的问题 蛋白酶。 RCDA（如果获得）将协助我实现目标 上面概括了两种方式。 首先，它将使我摆脱 部门义务，例如大量在职教学 课程，使我能够全身心投入研究 全年。 其次，通过获得这个奖项，我将 免除在其他委员会的服务，两个委员会均在 部门和机构级别。 生物化学与分子生物学系提供 为我的研究事业的发展提供支持性的环境。 新建立的肽合成/测序设施将 能够现场合成上述所需的肽 研究。 资源人员能够提供指导 还存在分子克隆技术。 事实是 系教师得到联邦的大力支持 授予机构意味着专业知识和设备很容易获得 通过周围地区积极的研究项目可以获得 实验室。 简而言之，路易斯安那州立大学的环境。提供了一个 进行研究的极其有利的环境 本提案中描述。 RCDA 的授予将极大地 加快完成这些研究的速度。