血红蛋白、一氧化氮与低氧性血管舒张的分子机制。
Hemoglobin, nitric oxide and molecular mechanisms of hypoxic vasodilation.
机构信息
Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, NC, USA.
出版信息
Trends Mol Med. 2009 Oct;15(10):452-60. doi: 10.1016/j.molmed.2009.08.002. Epub 2009 Sep 24.
Abstract
The protected transport of nitric oxide (NO) by hemoglobin (Hb) links the metabolic activity of working tissue to the regulation of its local blood supply through hypoxic vasodilation. This physiologic mechanism is allosterically coupled to the O(2) saturation of Hb and involves the covalent binding of NO to a cysteine residue in the beta-chain of Hb (Cys beta93) to form S-nitrosohemoglobin (SNO-Hb). Subsequent S-transnitrosation, the transfer of NO groups to thiols on the RBC membrane and then in the plasma, preserves NO vasodilator activity for delivery to the vascular endothelium. This SNO-Hb paradigm provides insight into the respiratory cycle and a new therapeutic focus for diseases involving abnormal microcirculatory perfusion. In addition, the formation of S-nitrosothiols in other proteins may regulate an array of physiological functions.
摘要
血红蛋白（Hb）对一氧化氮（NO）的保护运输将工作组织的代谢活性与局部血液供应的调节通过缺氧性血管舒张联系起来。这种生理机制与 Hb 的 O(2)饱和度变构偶联，并涉及 NO 与 Hbβ链中的半胱氨酸残基（Cys β93）的共价结合，形成 S-亚硝基血红蛋白（SNO-Hb）。随后的 S-转移亚硝酰化，即 NO 基团转移到 RBC 膜上的巯基，然后再转移到血浆中，将 NO 血管扩张活性保存下来并输送到血管内皮。SNO-Hb 范例为呼吸循环提供了深入了解，并为涉及异常微循环灌注的疾病提供了新的治疗重点。此外，其他蛋白质中 S-亚硝硫醇的形成可能调节一系列生理功能。
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