The Nitration of Proteins, Lipids and DNA by Peroxynitrite Derivatives-Chemistry Involved and Biological Relevance

Abstract

In recent years, much interest has been generated by the idea that nitrosative stress plays a role in the aetiology of human diseases, such as atherosclerosis, inflammation, cancer, and neurological diseases. The chemical changes mediated by reactive nitrogen species (RNS) are detrimental to cell function, because they can cause nitration, which can alter the structures of cellular proteins, DNA, and lipids, and hence, impair their normal function. One of the most potent biological nitrosative agents is peroxynitrite (ONOO−), which is produced when nitric oxide (•NO) and superoxide (•O2−) are combined at extremely rapid rates. Considering the plethora of oxidations by peroxynitrite, this makes peroxynitrite the most prevalent nitrating species responsible for protein, DNA, and lipids nitration in vivo. There is biochemical evidence to suggest that the interactions of the radicals NO and superoxide result in the formation of a redox system, which includes the reactions of nitrosation and nitration, and is a component of the complex cellular signalling network. However, the chemistry involved in the nitration process with peroxynitrite derivatives is poorly understood, particularly for biological molecules, such as DNA, proteins, and lipids. Here, we review the processes involved in the nitration of biomolecules, and provide a mechanistic explanation for the chemical reactions of NOS and nitrosative stress. This study reveals that these processes are based on a surprisingly simple and straightforward chemistry, with a fascinating influence on cellular physiology and pathology.