Polyamine Biosynthesis And Metabolism

多胺生物合成和代谢

• 批准号: 7593434
• 负责人: celia w tabor
• 金额: $ 24.66万
• 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/7593434
• 关键词: Amines; Anabolism; Cells; Condition; Differentiation and Growth; Enzymes; Escherichia coli; Growth; Life; Measures; Metabolism; Modification; Physiological; Polyamines; Protein Biosynthesis; Protein Overexpression; Purpose; Putrescine; Saccharomyces cerevisiae; Spermidine; Spermine; Structure; System; Techniques; Yeasts; beta-Alanine; hypusine; in vivo; interest; mutant; pantothenate

The polyamines, putrescine, spermidine, and spermine, are major polybasic compounds in all living cells. These amines are important for many systems related to growth and differentiation. For many years we have been studying how these polyamines are synthesized, how their biosynthesis and degradation are regulated, their physiologic functions, how they act in vivo, and the structure of the various biosynthetic enzymes. For this purpose we have constructed null mutants in each of the biosynthetic steps in both Escherichia coli and Saccharomyces cerevisiae, and have prepared overexpression systems for the biosynthetic enzymes. Our overall studies have aimed at the use of these mutants to elucidate the physiological functions of the polyamines. Our recent studies have been concerned with measuring the internal concentration of polyamines in Saccharomyces cerevisiae under various growth conditions, and, in particular, the internal concentration found when auxotrophic mutants are grown on limiting spermidine. These studies required modification of our analytical techniques to permit a more sensitive determination. We have found that the internal concentration of spermidine needed for growth is much less than the large amounts normally present in the cells, and that this lower concentration of spermidine is largely used for the biosynthesis of hypusine, a modification of eIF5A that is critical for protein biosynthesis. These studies are of particular significance since they demonstrated that this modification of eIF5A is the most critical function for spermidine; i.e. both for protein biosynthesis and growth. We have also been interested in investigating why the yeast cells (and other cells) normally contain the higher concentration of polyamines; i.e. much more than needed for growth. We have shown that one system requiring the larger amounts of spermidine and spermine is the biosynthesis of beta-alanine and pantothenate.

多胺，腐霉，精子和精子是所有活细胞中的主要多重化合物。这些胺对于许多与生长和分化有关的系统都很重要。多年来，我们一直在研究如何合成这些多胺，如何调节它们的生物合成和降解，它们的生理功能，它们在体内的作用以及各种生物合成酶的结构。为此，我们在大肠杆菌和酿酒酵母的每个生物合成步骤中构建了无效突变体，并为生物合成酶制备了过表达系统。我们的总体研究旨在使用这些突变体来阐明多胺的生理功能。 我们最近的研究一直涉及在各种生长条件下测量酿酒酵母中多胺的内部浓度，尤其是在限制精子时生长的可营养营养突变体时发现的内部浓度。这些研究需要修改我们的分析技术以允许更敏感的确定。 我们发现，生长所需的精子的内部浓度远小于通常存在的大量细胞，并且这种较低浓度的精子素在很大程度上被用于非偶然动物的生物合成，EIF5a的修饰对于蛋白质生物合成至关重要。这些研究特别重要，因为它们证明了EIF5A的这种修饰是精子定的最关键功能。即均用于蛋白质生物合成和生长。 我们也有兴趣研究为什么酵母细胞（和其他细胞）通常包含较高浓度的多胺浓度。即，增长所需的要多得多。 我们已经表明，需要大量的精子和精子需要的一个系统是β-丙氨酸和泛肽的生物合成。