Laboratory of Biophysics, Freiberg Instruments GmbH, 09599 Freiberg, Germany.
Free Radic Biol Med. 2017 Nov;112:544-552. doi: 10.1016/j.freeradbiomed.2017.08.025. Epub 2017 Sep 3.
While the biological role of nitric oxide (NO) synthase (NOS) is appreciated, several fundamental aspects of the NOS/NO-related signaling pathway(s) remain incompletely understood. Canonically, the NOS-derived NO diffuses through the (inter)cellular milieu to bind the prosthetic ferro(Fe)-heme group of the soluble guanylyl cyclase (sGC). The formation of ternary NO-ferroheme-sGC complex results in the enzyme activation and accelerated production of the second messenger, cyclic GMP. This paper argues that cells dynamically generate mobile/exchangeable NO-ferroheme species, which activate sGC and regulate the function of some other biomolecules. In contrast to free NO, the mobile NO-ferroheme may ensure safe, efficient and coordinated delivery of the signal within and between cells. The NO-heme signaling may contribute to a number of NOS/NO-related phenomena (e.g. nitrite bioactivity, selective protein S-(N-)nitrosation, endothelium and erythrocyte-dependent vasodilation, some neural and immune NOS functions) and predicts new NO-related discoveries, diagnostics and therapeutics.
虽然一氧化氮合酶 (NOS) 的生物学作用已被人们所认识，但 NOS/NO 相关信号通路的几个基本方面仍未完全理解。通常情况下，NOS 产生的一氧化氮 (NO) 通过（细胞间）细胞外环境扩散，与可溶性鸟苷酸环化酶 (sGC) 的亚铁血红素辅基结合。形成三元 NO-亚铁血红素-sGC 复合物导致酶的激活和第二信使环鸟苷酸 (cGMP) 的加速产生。本文认为，细胞动态生成可移动/可交换的 NO-亚铁血红素物质，这些物质可以激活 sGC 并调节其他一些生物分子的功能。与游离的 NO 不同，可移动的 NO-亚铁血红素可以确保信号在细胞内和细胞间的安全、高效和协调传递。NO-血红素信号可能与许多 NOS/NO 相关现象（如亚硝酸盐的生物活性、选择性蛋白质 S-（N-）硝化、内皮和红细胞依赖性血管舒张、一些神经和免疫 NOS 功能）有关，并预测新的与 NO 相关的发现、诊断和治疗方法。
