Nitric Oxide Reduction, Oxidation, and Mechanisms of Nitrosation

Nitric Oxide Reduction, Oxidation, and Mechanisms of Nitrosation 

As stated previously nitric oxide can react with other molecules to yield a number of secondary intermediates with different reactivities. However, it is important to bear in mind that nitric oxide has a relatively stable electronic configuration which limits direct reactions to three main types  

The second direct reaction pathway, one-electron reduction of a target by nitric oxide, could occur only if the target was itself a strong oxidant, since nitric oxide does not readily give up its unpaired electron. Oxidation of nitric oxide would result in the formation of NO, which would rapidly nitrosate nucleophiles such as amines, sulfhydryls, or aromatics. In fact, the best one-electron oxidants would be radicals such as -NOi or hydroxyl radical or even ONOO itself. In such cases the net effect would be nitric oxide addition reactions (nitrosations), regardless of whether the mechanism is considered to be transfer of an electron from nitric oxide followed by attack of NO or simple radical-radical combination. Thus, under most conditions, one-electron reduction of a target by nitric oxide becomes a simple addition reaction. 

Nitric oxide addition reactions and nitrosations (often referred to as nitrosylations) are currently the subject of much debate. Evidence exists that nitrosation, particularly thiol nitrosation, serves to prolong the biological activity of nitric oxide by acting as a slow-releasing reservior (Stamler et al, 1992 Keaney et al., 1993). It has also been proposed that alteration of the redox state of critical thiols by nitric oxide may serve a signaling function (Sucher and Lipton, 1991 Lipton et al., 1993) quite distinct from the ability of nitric oxide to directly stimulate cGMP production. 

It is here that the actual mechanisms of nitrosothiol formation become quite important. The mechanisms of nitrosothiol formation in vivo are 

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