Transnitrosation

Transnitrosation is defined as the transfer of NO (NO+) from one thiol to another without the generation of NO (Eq. (13)). 

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Recently nitrosamines have attracted attention because of their marked carcinogenic activity in a wide variety of animal species Q, ). Nitrosamines are likely to be carcinogens in man as well human exposure to these compounds is by ingestion, inhalation, dermal contact and vivo formation from nitrite and amines Nitrite and amines react most rapidly at an acidic pH A variety of factors, however, make nitrosation a potentially important reaction above pH 7 these include the presence of microorganisms, and the possibilities of catalysis by thiocyanate, metals and phenols, and of transnitrosation by other nitroso compounds. 

Smoking. The effects of smoking on the formation of N-nitros-amines in bacon has been investigated recently by Bharucha et al. ( ). They reported that unsmoked bacon samples generally tended to contain more N-nitrosamines, presumably because of their higher nitrite content at the time of frying. Sink and Hsu (55) showed a lowering of residual nitrite in a liquid smoke dip process for frankfurters when the pH also was lowered. The effects of smoke seem to be a combination of pH decrease and direct C-nitrosation of phenolic compounds to lower the residual nitrite in the product (56). This is an area which requires further study since certain C-nitrosophenols have been shown to catalytically transnitrosate amines in model systems (57). 

Further, the protein bound nitrite represents a substantial pool of nitrosating ability that may function in transnitrosation (, 23,... 

Methylanaline could be transnitrosated with nitrite and S-nitrosocysteine and also by a simulated protein bound nitrite. In the latter case, an important factor was the local concentration of nitrosothiol groups on the matrix. The effects of S-nitrosocysteine as an inhibitor of lipid oxidation, as a color developer, and as an anticlostridial, have been reported recently in a turkey product (31). The Molar concentration of RSNO equating to 25 ppm nitrite gave similar results for color and inhibition of lipid oxidation but had less anti-clostridial activity. Transnitrosation between RSNO and heme protein was demonstrated. 

Based on computational studies and mass spectral evidence Houk and colleagues (2003) have proposed that transnitrosation proceeds through a nitroxyldisufide intermediate (Scheme 4.2 b)... 

Thiols, protein or small molecular weight, can be S-nitrosated either by reaction with N O-oxidation products (Scheme 4.1) in hydrophobic domains of plasma proteins or transnitrosated at the cell-plasma interface of NO-producing cells (endothelial cells) or NO-storing cells (RBCs). Efforts to determine the true levels in plasma and in the various cellular compartments are complicated owing to thermal sensitivity and photosensitivity (Sexton et al., 1994 Alpert et al., 1997 Mutus et al., 1999) of the RS-NO bond. Techniques currently employed for the detection and quantification of RSNOs have been summarized in recent reviews (Martinez Riuz and Lamas, 2004 Rasaf et al., 2004). 

Zai, A., Rudd, M. A., Scribner, A. W., Loscalzo, J., Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates intracellular transfer of nitric oxide, J. Clin. Invest. 103 (1999), p. 393-399... 

In addition, S-nitroso thiols can act as NO+ donors in S-transnitrosation reactions, which are of great physiological significance, or they can release NO when reacting with thiols [49] [50]. A further mechanism exists for S-ni-trosoglutathione, which is a substrate of glutathione peroxidase. In this case, the enzyme catalyzes the release of NO or a reaction of transnitrosation [51]. 

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 ). 

A few reactions of A-nitrosopiperazines have been reported recently. At least some such piperazines undergo facile transnitrosation and may be used to nitrosate other secondary bases or the like. For example, 2,6-dimethyl-1,4-dinitrosopiperazine (31) with piperidine (32), at pH 1.7 in the presence of sodium thiocyanate as catalyst, gave 2,6-dimethyl-4-nitrosopiperazine (33) and 1-nitrosopiperidine (34).763,cf-954... 

S-Nitrosothiols undergo a reversible transnitrosation reaction at zinc tris(pyrazolyl)boratozinc thiolates, " TpZn-SR. These zinc thiolates are rmreactive toward anaerobic NO but rapidly react with NO in the presence of O2 or anaerobically with NO2 to release the S-nitrosothiol RSNO with formation of the corresponding zinc nitrate 125). 

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). 

Zai A, Rudd MA, Scribner AW, Loscalzo J. 1999. Cell-surface protein disulfide isomerase catalyzes transnitrosation... 

The reagent can be used to effect transnitrosation of secondary amines. Thus N-methylaniline on being refluxed with the reagent in benzene for 20 min. afforded... 

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