Carbon dioxide: Physiological catalyst for peroxynitrite-mediated cellular damage or cellular protectant?
Carbon dioxide: Physiological catalyst for peroxynitrite-mediated cellular damage or cellular protectant?
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DOI：
10.1021/tx960046z
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发表时间：
1996-07-01
影响因子：
4.1
通讯作者：
Hurst, JK
中科院分区：
文献类型：
--
作者：
Lymar, SV;Hurst, JK
The discovery (1, 2) that NO combines rapidly with O2-to form the strongly oxidizing peroxynitrite adduct1 has stimulated tremendous interest among researchers concerned with phagocytic cell function and with oxidative stress and its biomedical implications. Certain organelles (eg, the endothelium, neuronal tissues, macrophages) appear capable of simultaneously generating O2-and NO, and thus, of forming this potentially destructive peroxide (3). Subsequent modeling studies have shown that ONO2 reacts moderately rapidly with a variety of biological compounds including thiols (4, 5) and thioethers (6, 7), ascorbic acid (8, 9), amino acids bearing aromatic substituents (10-12), and lipidic components of membranes (13), that ONO2H is a good substrate for peroxidases (14), and that ONO2 is toxic to microbes (15-17). In several of these studies there was indication that bicarbonate could dramatically alter the reactivity characteristics of ONO2 (11, 14, 18, 19), but this effect was not quantitatively investigated. Quite recently, we have shown that CO2 derived from bicarbonate reacts rapidly with ONO2-, apparently forming an ONO2CO2-adduct (20). Bicarbonate is a ubiquitous component of biological fluids, being present at the relatively high concentration levels of 24 mM or greater (21). As outlined below, the rate of its reaction with ONO2 is projected to be sufficiently large that virtually all of the ONO2 that might be produced in peroxidase-free biological environments will form the ONO2CO2-adduct. Accordingly, the reaction between NO and O2-should be considered as just the first step in the overall sequence: and efforts to evaluate the putative biological roles of peroxynitrite should really be focused upon the chemical properties of ONO2CO2-and secondary oxidants that might be derived from it, rather than the reactivity of ONO2 itself toward potential biological targets. This point will be illustrated in the following discussion of our studies on the role of CO2 in ONO2-mediated oxidation of tyrosine (22) and bacterial killing. 2
