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膜对一氧化氮自氧化和亚硝化作用的加速

Acceleration of nitric oxide autoxidation and nitrosation by membranes.

作者信息

Möller Matias N, Li Qian, Lancaster Jack R, Denicola Ana

机构信息

Laboratorio de Fisicoquímica Biológica, Facultad de Ciencias, and Center for Free Radical and Biomedical Research, Universidad de la República, Montevideo, Uruguay.

出版信息

IUBMB Life. 2007 Apr-May;59(4-5):243-8. doi: 10.1080/15216540701311147.

Abstract

The reaction between nitric oxide ((.)NO) and oxygen yields reactive species capable of oxidizing and nitrosating proteins, as well as deaminating DNA bases. Although this reaction is considered too slow to be biologically relevant, it has been shown that membranes, lipoproteins, mitochondria and possibly proteins can accelerate this reaction. This effect stems from the higher solubility of both (.)NO and O(2)in the hydrophobic phase of these biological particles, leading to a concentration of both reagents and so a higher rate of reaction. It has been determined that this reaction occurs from 30 to 300 times more rapidly within the membrane, while even higher values have been suggested for proteins. The autoxidation of (.)NO in membranes is not the main route for cellular (.)NO consumption but an important consequence of this phenomenon is to focus the generation of significant amounts of oxidizing and nitrosating molecules (nitrogen dioxide and dinitrogen trioxide) in the small volume comprised by cellular membranes. Even so, these reactive species are diffusible and their ultimate fate will depend on the reactivity towards available substrates rather than on physical barriers. The acceleration of (.)NO autoxidation by biological hydrophobic phases may thus be a general phenomenon that increases in importance in cases of (.)NO overproduction.

摘要

一氧化氮(·NO)与氧气之间的反应会产生能够氧化和亚硝化蛋白质以及使DNA碱基脱氨基的活性物质。尽管该反应被认为过于缓慢,在生物学上不具有相关性,但研究表明,细胞膜、脂蛋白、线粒体以及可能还有蛋白质都能加速这一反应。这种效应源于·NO和O₂在这些生物颗粒疏水相中的更高溶解度,导致两种反应物浓度增加,从而使反应速率更高。据测定,该反应在膜内发生的速度比膜外快30至300倍,而对于蛋白质,甚至有更高的数值。膜中·NO的自氧化并非细胞内·NO消耗的主要途径,但这一现象的一个重要后果是,在细胞膜所包含的小体积内集中产生大量的氧化和亚硝化分子(二氧化氮和三氧化二氮)。即便如此,这些活性物质是可扩散的,它们的最终命运将取决于对可用底物的反应性,而非物理屏障。因此,生物疏水相对·NO自氧化的加速作用可能是一种普遍现象,在·NO产生过量的情况下其重要性会增加。

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