HYPUSINE IN EIF-4D--BIOSYNTHESIS AND FUNCTION

真核蛋白质翻译启动因子5A(eIF-5A)含有一个 残留物，似乎是唯一具有 这种独特的氨基酸。Hypusine是由翻译后产生的 将多胺亚精胺的丁胺部分转移到 EIF-5A前体中的赖氨酸残基形成脱氧亚硫氨酸 羟化作用形成下苏氨酸。这些发现揭示了一种新的细胞 代谢途径。Hypusine是生物活性必不可少的物质。 体外翻译启动实验中的eIF-5A和催产素和eIF-5A 5A似乎是真核细胞生长的重要元素。因此， 亚硫氨酸的生物合成步骤、脱氧亚硫氨酸的合成和 脱氧亚硫氨酸羟化呈现特殊的潜在靶点 干预细胞增殖。几种血管紧张素转换酶抑制剂 脱氧硫氨酸合成酶和脱氧硫氨酸羟基酶 已经开发出来，并检测了它们的细胞效应。研究是 正在进行将下丘脑的结构与生理的 EIF-5A在哺乳动物细胞中的功能。

Eukaryotic protein translation iniation factor 5A (eIF-5A) contains one residue of hypusine and appears to be the only cellular protein with this unique amino acid. Hypusine is produced post-translationally by transfer of the butylamine portion of the polyamine spermidine to a lysine residue in the eIF-5A precursor to form deoxyhypusine followed by hydroxylation to form hypusine. These findings reveal a novel cellular metabolic pathway. Hypusine is essential for the biological activity of eIF-5A in an in vitro translation initiation assay and hypusine and eIF- 5A appear to be vital elements for growth of eukaryotic cells. Thus, the hypusine biosynthetic steps, deoxyhypusine synthesis and deoxyhypusine hydroxylation present special potential targets for intervention in cellular proliferation. Several inhibitors of the enzymes deoxyhypusine synthase, and deoxyhypusine hydroxylase were developed and their cellular effects have been examined. Studies are underway to relate the structure of hypusine to the physiological function of eIF-5A in mammalian cells.