Transnitrosating agent

The denitrosation reaction was also examined, using hydrazine as a trap for free nitrous acid. A range of denitrosation reactions have been studied together with the reactivity of thiourea, alkylthioureas, cysteine, glutathione, 5-methyl-cysteine and methionine toward A -methyl-A -nitrosoaniline. The results are consistent with an initial rate-determining 5-nitrosation of the thiourea by the protonated nitrosamine. Alicyclic nitrosamines and nitrosoamino acids have also been considered as transnitrosating agents. 

Chemists have long been aware that amines can react with various nitrosating agents, under a variety of conditions, to form a wide array of N-nitroso derivatives (1 ). It was generally assumed that only secondary amines can effectively form stable N-nitrosamines. However, it has now become apparent that primary and tertiary amines, as well as tetraalkylammonium salts, can all form N-nitroso derivatives under the appropriate reaction conditions (2-10). It has also become apparent that there are several mechanisms possible for the formation of the most common N-nitroso derivatives. Thus, in addition to the more customary reaction of an amine with nitrous acid, N-nitroso derivatives can also form via the reaction of an amine with NO (NO2, N2O3, N2O4) ( ). Amines can also be transnitrosated with already formed N-N-nitroso or C-nitro compounds via a transnitrosation reaction, they can be converted into their N-nitroso derivatives ). 

Many pathways exist to generate a nitrosothiol in vitro by the 1-electron oxidation of NO. Nitrosothiols can be formed via the reaction of a thiol with N2O3, a nitrosating agent that is an intermediate in the decomposition of NO in aerobic solution, or via the direct reaction of NO with a thiol to form an addition complex (SNO ) followed by a 1-electron oxidation. S-nitrosation of a protein thiol also can occur by a trans-S-nitrosation event from a low molecular weight nitrosothiol, such as S -nitrosoglutathione, or from a nitrosated protein cysteine (8). Whereas the in vivo mechanism of protein S -nitrosation is unknown, a protein-mediated trans-S -nitrosation mechanism is an attractive possibility because of the specificity it could impart on the reaction. Additionally, the same protein could catalyze both the nitrosation and denitrosation of a specific cysteine. A report showing that the protein thioredoxin can transnitrosate caspase-3 selectively and reversibly lends support to this proposal (34). 

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