Reactions of nitrogen dioxide in aqueous model systems: oxidation of tyrosine units in peptides and proteins
WA Prütz, H Mönig, J Butler, EJ Land - Archives of biochemistry and …, 1985 - Elsevier
WA Prütz, H Mönig, J Butler, EJ Land
Archives of biochemistry and biophysics, 1985•ElsevierBy application of pulse radiolysis it was demonstrated that nitrogen dioxide (NO 2 ̇)
oxidizes Gly-Tyr in aqueous solution with a strongly pH-dependent rate constant (k 6= 3.2×
10 5 M− 1 S− 1 at pH 7.5 and k 6= 2.0× 10 7 M− 1 S− 1 at pH 11.3), primarily generating
phenoxyl radicals. The phenoxyl can react further with NO 2 ̇ (k 7~ 3× 10 9 M− 1 S− 1) to
form nitrotyrosine, which is the predominant final product in neutral solution and at low
tyrosyl concentrations under gamma-radiolysis conditions. Tyrosine nitration is less efficient …
oxidizes Gly-Tyr in aqueous solution with a strongly pH-dependent rate constant (k 6= 3.2×
10 5 M− 1 S− 1 at pH 7.5 and k 6= 2.0× 10 7 M− 1 S− 1 at pH 11.3), primarily generating
phenoxyl radicals. The phenoxyl can react further with NO 2 ̇ (k 7~ 3× 10 9 M− 1 S− 1) to
form nitrotyrosine, which is the predominant final product in neutral solution and at low
tyrosyl concentrations under gamma-radiolysis conditions. Tyrosine nitration is less efficient …
By application of pulse radiolysis it was demonstrated that nitrogen dioxide (NO 2 ̇) oxidizes Gly-Tyr in aqueous solution with a strongly pH-dependent rate constant (k 6= 3.2× 10 5 M− 1 S− 1 at pH 7.5 and k 6= 2.0× 10 7 M− 1 S− 1 at pH 11.3), primarily generating phenoxyl radicals. The phenoxyl can react further with NO 2 ̇ (k 7~ 3× 10 9 M− 1 S− 1) to form nitrotyrosine, which is the predominant final product in neutral solution and at low tyrosyl concentrations under gamma-radiolysis conditions. Tyrosine nitration is less efficient in acidic solution, due to the natural disproportionation of NO 2 ̇, and in alkaline solutions and at high tyrosyl concentrations due to enhanced tyrosyl dimerization. Selective tyrosine nitration by interaction of NO 2 ̇ with proteins (at pH 7 to 9) was demonstrated in the case of histone, lysozyme, ribonuclease A, and subtilisin Carlsberg. Nitrotyrosine developed slowly also under incubation of Gly-Tyr with nitrite at pH 4 to 5, where NO 2 ̇ is formed by acid decomposition of HONO. It is recalled in this context that NO 2 ̇-induced oxidations, by regenerating NO 2 ̇, can propagate NO 2 ̇ NO 2− redox cycling under acidic conditions. Even faster than with tyrosine is the NO 2 ̇-induced oxidation of cysteine-thiolate (k 9= 2.4× 10 8 M− 1 S− 1 at pH 9.2), involving the transient formation of cystinyl radical anions. The interaction of NO 2 ̇ with Gly-Trp was comparably slow (k~ 10 6 M− 1 S− 1), and no reaction was detectable by pulse radiolysis with Met-Gly and (Cys-Gly) 2, or with DNA. Slow reactions of NO 2 ̇ were observed with arachidonic acid (k~ 10 6 M− 1 S− 1 at pH 9.0) and with linoleate (k~ 2× 10 5 M− 1 S− 1 at pH 9.4), indicating that NO 2 ̇ is capable of initiating lipid peroxidation even in an aqueous environment. NO 2 ̇-Induced tyrosine nitration, using 50 μ m Gly-Tyr at pH 8.2, was hardly inhibited, however, in the presence of 1 mM linoleate, and was not affected at all in the presence of 5 mM dimethylamine (a nitrosamine precursor). It is concluded that protein modifications, and particularly phenol and thiol oxidation, may be an important mechanism, as well as initiation of lipid peroxidation, of action of NO 2 ̇ in biological systems.
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