BIOLOGICAL ACTIVITY OF N-HYDROXY-L-ARGININE

描述(研究人员摘要)：N-羟基-L-精氨酸是一种 氨基酸生物合成一氧化氮(NO)的中间体 L-精氨酸。这个反应是由一氧化氮合酶催化的。 (否)。用纯化的一氧化氮合酶进行的早期酶学研究表明，NHA是 在酶的周转过程中不释放，因此不应达到 显著的细胞内浓度。然而，最近的数据显示 全细胞实验表明，与之前的看法相反，NHA是 由一氧化氮合酶释放，然后可以离开细胞并达到极高的水平 在细胞外空间。因为这种现象不太可能代表 没有生物合成的固有低效，NHA必须提供生理上的 功能。因为已经发现NHA的释放在NOS中具有重要意义 在感染或寄生虫入侵期间诱导的异构体，它很可能 NHA参与了免疫反应。因此，这一目标是 建议研究NHA在免疫中的生理作用 回应。初步数据表明NHA可能起到抑制细胞的作用 基于其与酶的相互作用的几种机制的增殖 精氨酸酶。了解NHA的作用机制可能会导致 新的和独特的治疗策略的发展 感染或癌症。

DESCRIPTION (Investigator's Abstract): N-Hydroxy-L-arginine (NHA) is an intermediate in the biosynthesis of nitric oxide (NO) from the amino acid L-arginine. This reaction is catalyzed by the enzyme nitric oxide synthase (NOS). Early enzymological work using purified NOS indicated that NHA was not released during enzyme turnover and therefore should not reach significant intracellular concentrations. However, more recent data in whole cell experiments indicates that, contrary to previous beliefs, NHA is released by NOS and can then leave the cell and reach extremely high levels in extracellular space. As it is unlikely that this phenomenon represents an inherent inefficiency in NO biosynthesis, NHA must serve a physiological function. Since NHA release has been found to be significant from the NOS isoform which is induced during infection or parasite invasion, it is likely that NHA is involved in the immune response. Thus, the goal of this proposal is to investigate the physiological role of NHA in the immune response. Preliminary data indicate that NHA may serve to inhibit cell proliferation by several mechanisms based on its interaction with the enzyme arginase. An understanding of the mechanism of action of NHA may lead to the development of novel and unique strategies for the treatment of infection or cancer.