Proline, nitrosation

Evidence exists that the relative solubility of amines and inhibitors in heterogeneous oil-water systems could be decisive in formation of nitrosamines and blocking these reactions, Nitrosopyrrolidine formation in bacon predominates in the adipose tissue despite the fact that its precursor, proline, predominates in the lean tissue (5,6,7). Mottram and Patterson (8) partly attribute this phenomenon to the fact that the adipose tissue furnishes a medium in which nitrosation is favored, Massey, et al, (9) found that the presence of decane in a model heterogeneous system caused a 20-fold increase in rate of nitrosamine formation from lipophilic dihexylamine, but had no effect on nitrosation of hydrophilic pyrrolidine. Ascorbic acid in the presence of decane enhanced the synthesis of nitrosamines from lipophilic amines, but had no effect on nitrosation of pyrrolidine. The oil-soluble inhibitor ascorbyl palmitate had little influence on the formation of nitrosamines in the presence or absence of decane. 

How proline is converted to NPYR has not yet been fully elucidated and could conceivably occur by either of two pathways (29, ). One pathway involves the initial N-nitrosation of proline, followed by decarboxylation, while in the other, proline is first decarboxylated to pyrrolidine followed by N-nitrosation to NPYR. Since the conversion of N-nitrosoproline (NPRO) to NPYR occurs at a much lower temperature than the transformation of proline to pyrrolidine, the pathway involving intermediacy of NPRO is thus the more likely route ( ). It has been reported that preformed NPRO in raw bacon is not the primary precursor of NPYR in cooked bacon (29,33-5), as shown by the fact that ascorbyl paImitate, when added to bacon, inhibits the formation of NPYR (33). However, this by no means rules out the intermediacy of NPRO which could be formed at the higher temperatures attained during the frying process (29,36). 

Amino acids undergo similar nitrosation reactions to yield hydroxy acids or lactones. Diamino acids tend to yield cyclic imino acids, so that ornithine and lysine give rise to proline and pipecolic acid, respectively. 

For both the in vitro studies with morpholine and pyrrolidine and the in vivo study with proline, it was observed that partially decomposed [Fe2(SMe)2(NO)4] was a much more potent nitrosation agent than the pure complex (110). The nature of the decomposition was not reported, and it is not clear what the significance of this report may be, although nitrite was probably present in the decomposed material. 

Scott et al. (3566) and Brunnemann et al. (511) reported that cigarette and chewing tobaccos differed in their NPRO levels Cigarette tobacco contained 2 ppm (less than 1% of free proline was nitrosated), chewing tobacco contained about 35 ppm (up to 40% of free proline was nitrosated). They reported that the NPRO level is dependent on proline level, nitrate level, and curing method. 

The nitrosation of -amino acids is especially interesting because of the biological importance of N-nitrosoamines (see Sect. 4.2). The nitrosation mechanism was investigated first with amino acids containing a secondary amino group, namely proline (4.1, X = H), 4-hydroxyproline (4.1, X = OH), and sarcosine (4.2), but also with cysteine (4.3). 

Fig. 1 Posttranslational redox modificatitnis to amino acids in proteins. Many amino acids can undergo various posttranslatiraial redox modifications in the presence of NAPQI, oxidative stress, and nitrosative stress. Thiols in cysteine can undergo covalent binding, mixed disulfide formation, nitrosylation, and become oxidized to sulfenic, sulfinic, and sulfonic acids. Tyrosine can become nitrated by peroxynitrate, and methionine can be oxidized by ROS to methionine sulfoxide. Not shown are many other oxidatirais that can occur to other amino acids such as proline, histidine, etc.

From the aspect of chemical carcinogenity the polarographic determination of N-nitrosamines become important. These compounds may be present in food, beverages and atmosphere, occasionally they can be formed in the body by nitrosation of amines, especially in the stomach. There were many papers published describing the determination of various nitrosamines (derivatives of proline, pyrolidine, piperidine, etc.) in different matrices[26]. The most important problem in their analysis (as with the... 

Oshima, H., and Bartsch, H., 1981, Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitroso-proline excreted in the urine. Cancer Res. 41 3658-3662. 

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