POLYAMINE BIOSYNTHESIS AND FUNCTION

多胺生物合成和功能

• 批准号: 6105121
• 负责人: Herbert Tabor
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 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/6105121
• 关键词: Escherichia coli; S adenosylmethionine; Saccharomyces cerevisiae; biosynthesis; decarboxylases; enzyme activity; enzyme structure; microorganism genetics; microorganism growth; mitochondria; molecular cloning; ornithine decarboxylase; oxidative stress; protein biosynthesis; putrescine; spermidine

The polyamines, putrescine, spermidine, and spermine, are major polybasic compounds in all living cells. These amines have been shown to be important for many systems related to growth and differentiation. We have been interested in how these polyamines are synthesized, how their biosynthesis and degradation are regulated, their physiologic functions, and how they act in vivo. For this purpose we have constructed null mutants in each of the biosynthetic steps in both Escherichia coli and in Saccharomyces cerevisiae.. Our present studies are directed at extending our studies on the biochemistry, regulation and genetics of these amines and of the biosynthetic enzymes in S. cerevisiae. During the current year we have been particularly interested in studying the regulation of the enzyme ornithine decarboxylase which is a key enzyme in the formation of the polyamines, and is of special interest in studies on the physiological function of the polyamines. The ornithine decarboxylase levels are repressed by the addition of spermidine to the medium, and we have found that, contrary to previous reports in the literature, an important part of this regulation involves the induction of a proteolytic activity. Interestingly this induction does not occur if protein synthesis is inhibited, indicating the involvement of a new, and, as yet unidentified, protein. Other studies have involved: (1) the effect of polyamine deficiency on the ribosomal pattern as part of our ongoing studies on the role of the polyamines in protein biosynthesis, and (2) in collaboration with Arthur Kornberg a quantitative comparison of polyamine levels and polyphosphate levels in E. coli and S. cerevisiae, using our polyamine-requiring mutants and Kornberg's mutants in the polyphosphate pathways in yeast.

多胺、腐胺、亚精胺和 精胺是所有活细胞中的主要多元化合物。这些 胺已被证明对许多相关系统很重要 到生长和分化。我们一直感兴趣的是这些 多胺的合成及其生物合成和降解 的调节、它们的生理功能以及它们在体内的作用。 为此，我们在每个中构建了无效突变体 大肠杆菌和酵母菌中的生物合成步骤 cerevisiae..我们目前的研究旨在扩展我们的 这些胺的生物化学、调控和遗传学研究 以及酿酒酵母中的生物合成酶。当前期间 今年我们对研究法规特别感兴趣 鸟氨酸脱羧酶是生物体内的关键酶 多胺的形成，并且对以下方面的研究特别感兴趣 多胺的生理功能。鸟氨酸 通过添加亚精胺来抑制脱羧酶水平 媒体，我们发现，与之前的报道相反 在文献中，该规定的一个重要部分涉及 诱导蛋白水解活性。有趣的是，这个归纳确实 如果蛋白质合成受到抑制则不会发生，表明参与 一种新的、尚未鉴定的蛋白质。其他研究有 涉及：（1）多胺缺乏对核糖体的影响 模式作为我们正在进行的多胺作用研究的一部分 蛋白质生物合成，以及 (2) 与 Arthur 合作 科恩伯格对多胺水平和 大肠杆菌和酿酒酵母中的多磷酸盐水平，使用我们的 需要多胺的突变体和科恩伯格突变体 酵母中的多磷酸途径。