Reactivity of Amino Acids in Nitrosation Reactions and Its Relation to the Alkylating Potential of Their Products
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- 作者：M. del Pilar Garcí ; a-Santos ; Samuel Gonzá ; lez-Mancebo ; Jesú ; s Herná ; ndez-Benito ; Emilio Calle ; and Julio Casado
- 刊名：Journal of the American Chemical Society
- 出版年：2002
- 出版时间：March 13, 2002
- 年：2002
- 卷：124
- 期：10
- 页码：2177 - 2182
- 全文大小：101K
- 年卷期：v.124,no.10(March 13, 2002)
- ISSN：1520-5126
文摘
Nitrosation reactions of amino acids with an -NH2 group [namely, six 
-amino acids (glycine,alanine, -aminobutyric acid, -aminoisobutyric acid, valine, and norvaline); two 
-amino acids (-alanineand -aminobutyric acid), and one 
-amino acid (-aminobutyric acid)] were studied. Nitrosation was carriedout in aqueous acid media, mimicking the conditions of the stomach lumen. The rate equation was r =k3 exp[amino acid][nitrite]2, with a maximum k3 exp value in the 2.3-2.7 pH range. The existence of an isokineticrelationship supports the argument that all the reactions share a common mechanism. A nitrosationmechanism is proposed, and the following conclusions are drawn: (i) Nitrosation reactions of amino acidswith a primary amino group in acid media occur with dinitrogen trioxide as the main nitrosating agent. Thefinding that the nitrosation rate is proportional to the square of the nitrite concentration suggests that theyield of nitrosation products in the stomach would increase sharply with higher nitrate/nitrite intakes. (ii)Stomach hypochlorhydria could be a potential enhancer of in vivo amino acid nitrosation. (iii) The reactivity(k3 exp) [-amino acids > -amino acids > -amino acids] is the same as that found in a previous work forthe alkylating potential of lactones formed from nitrosation products of the same amino acids. This impliesthat the nitrosation reactions of the most common natural amino acids are the most efficient precursors ofthe most powerful alkylating agents. (iv) The order of magnitude (107-108 M-1 s-1) of the bimolecular rateconstants of nitrosation shows that such reactions occur through an encounter process.
-amino acids (glycine,alanine, -aminobutyric acid, -aminoisobutyric acid, valine, and norvaline); two -amino acids (-alanineand -aminobutyric acid), and one -amino acid (-aminobutyric acid)] were studied. Nitrosation was carriedout in aqueous acid media, mimicking the conditions of the stomach lumen. The rate equation was r =k3 exp[amino acid][nitrite]2, with a maximum k3 exp value in the 2.3-2.7 pH range. The existence of an isokineticrelationship supports the argument that all the reactions share a common mechanism. A nitrosationmechanism is proposed, and the following conclusions are drawn: (i) Nitrosation reactions of amino acidswith a primary amino group in acid media occur with dinitrogen trioxide as the main nitrosating agent. Thefinding that the nitrosation rate is proportional to the square of the nitrite concentration suggests that theyield of nitrosation products in the stomach would increase sharply with higher nitrate/nitrite intakes. (ii)Stomach hypochlorhydria could be a potential enhancer of in vivo amino acid nitrosation. (iii) The reactivity(k3 exp) [-amino acids > -amino acids > -amino acids] is the same as that found in a previous work forthe alkylating potential of lactones formed from nitrosation products of the same amino acids. This impliesthat the nitrosation reactions of the most common natural amino acids are the most efficient precursors ofthe most powerful alkylating agents. (iv) The order of magnitude (107-108 M-1 s-1) of the bimolecular rateconstants of nitrosation shows that such reactions occur through an encounter process.