REGULATION OF ALBUMIN SYNTHESIS BY AMINO ACIDS

氨基酸对白蛋白合成的调节

• 批准号: 3169093
• 负责人: BARRY E LEDFORD
• 金额: $ 10.04万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-04-15 至 1987-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3169093
• 关键词: adenosine; alpha fetoprotein; cell bank /registry; cell free system; essential aminoacid; genetic translation; hepatocellular carcinoma; immunochemistry; isoleucine; liver metabolism; messenger RNA; nutrition related tag; radioimmunoassay; radiotracer; ribosomes; tryptophan; ultracentrifugation; valine

The in vivo sythesis of serum albumin by liver has been shown to be specifically controlled by plasma levels of essential amino acids, especially tryptophan. The apparent relative stability of the albumin mRNA would suggest that these amino acid effects occur at the translational level. The overall aim of this research project is to analyze the effects of essential amino acid limitation on albumin synthesis, and to investigate the possibility of exogenous albumin as a source of essential amino acids. The focus of these studies will be a highly differentiated mouse hepatoma cell line, Hepa, which continues to secrete the serum proteins, albumin, alpha-fetoprotein, transferring, and complement C3b inactivator. The initial phase of the project will involve the systematic manipulation of culture media concentrations of tryptophan, histidine, isoleucine, leucine, and phenylalanine. Absolute rates (molecules/cells/min) of albumin secretion will be measured by radioimmunoassay. The specificity of amino acid effects on albumin synthesis will be assessed by comparison with other serum proteins and total cellular protein. Kinetic analysis of albumin and total protein synthesis will include measurements of: (1)\relative and absolute (albumin) rates of synthesis; (2)\ribosome transit times; and (3)\number-average polyribosome sizes. From these data mRNA translational efficiencies (initiation rates) and relative and absolute (albumin) cellular contents of functional mRNAs will be calculated. The data will be interpreted in terms of general translational control models. (G)

肝脏血清白蛋白的体内体育学已显示为 特别由血浆水平的必需氨基酸水平控制， 特别是色氨酸。 白蛋白mRNA的明显相对稳定性 会表明这些氨基酸作用发生在翻译处 等级。 该研究项目的总体目的是分析效果 白蛋白合成的必需氨基酸限制，并研究 外源白蛋白作为必需氨基酸的来源的可能性。 这些研究的重点将是高度分化的小鼠肝癌 细胞系，HEPA，继续分泌血清蛋白，白蛋白， α-五蛋白，转移和补体C3B灭活剂。 这 该项目的初始阶段将涉及系统的操纵 色氨酸，组氨酸，异亮氨酸，亮氨酸的培养基浓度 和苯丙氨酸。 白蛋白的绝对速率（分子/细胞/分子） 分泌将通过放射免疫测定法测量。 氨基的特异性 通过与其他相比，将评估对白蛋白合成的酸影响 血清蛋白和总细胞蛋白。 白蛋白和动力学分析 总蛋白质合成将包括：（1）\相对和 合成的绝对（白蛋白）速率； （2）\核糖体运输时间；和 （3）\数字 - 多核糖体大小。 从这些数据mRNA翻译中 效率（起始率）和相对和绝对（白蛋白） 将计算功能mRNA的细胞含量。 数据将是 用一般翻译控制模型来解释。 （g）