BIOLOGICAL ACTIVITY OF N-HYDROXY-L-ARGININE

描述（研究者摘要）：N-羟基-L-精氨酸（NHA）是一种 一氧化氮（NO）生物合成的中间体， L-精氨酸 这个反应是由一氧化氮合酶催化的 （NOS）。 使用纯化NOS的早期酶学工作表明，NHA是 在酶周转期间不释放，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，与以前的信念相反，NHA是 由NOS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 由于NO生物合成中固有的低效率，NHA必须起到生理作用， 功能 由于已发现NHA释放与NOS显著相关， 在感染或寄生虫入侵期间诱导的同种型， NHA参与了免疫反应 因此， 建议是研究NHA在免疫中的生理作用， 反应 初步数据表明，NHA可能有助于抑制细胞 基于其与酶的相互作用，通过几种机制进行增殖 精氨酸酶。 了解NHA的作用机制可能会导致 开发新颖独特的治疗策略， 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.