The oxyhemoglobin reaction of nitric oxide

作     者：Gow, AJ Luchsinger, BP Pawloski, JR Singel, DJ Stamler, JS 

作者机构：Duke Univ Med Ctr Howard Hughes Med Inst Durham NC 27710 USA Duke Univ Med Ctr Dept Med Durham NC 27710 USA Montana State Univ Dept Chem & Biochem Bozeman MT 59717 USA Duke Univ Dept Cell Biol Durham NC 27710 USA 

出 版 物：《PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA》 (美国国家科学院汇刊)

年 卷 期：1999年第96卷第16期

页      面：9027-9032页

核心收录：

学科分类：07[理学] 08[工学] 

基　　金：NHLBI NIH HHS [R01 HL059130  HL52529  HL59130] Funding Source: Medline 

主　　题：电子自旋共振谱学 红细胞/生理学 动力学 模型 化学 一氧化氮/化学 一氧化氮/代谢 氧合血红蛋白/化学 氧合血红蛋白/代谢 分光光度法 超氧化物类/血液 人类 

摘      要：The oxidation of nitric oxide (NO) to nitrate by oxyhemoglobin is a fundamental reaction that shapes our understanding of NO biology. This reaction is considered to be the major pathway for NO elimination from the body;it is the basis for a prevalent NO assay;it is a critical feature in the modeling of NO diffusion in the circulatory system;and it informs a variety of therapeutic applications, including NO-inhalation therapy and blood substitute design. Here we show that, under physiological conditions, this reaction is of little significance. Instead, NO preferentially binds to the minor population of the hemoglobin s vacant hemes in a cooperative manner, nitrosylates hemoglobin thiols, or reacts with liberated superoxide in solution. In the red blood cell, superoxide dismutase eliminates superoxide, increasing the yield of S-nitrosohemoglobin and nitrosylated hemes, Hemoglobin thus serves to regulate the chemistry of NO and maintain it in a bioactive state. These results represent a reversal of the conventional view of hemoglobin in NO biology and motivate a reconsideration of fundamental issues in NO biochemistry and therapy.