Tyrosine nitration by simultaneous generation of (.)NO and O-(2) under physiological conditions. How the radicals do the job.
Radiation chemical experiments demonstrate that the reaction of tyrosyl radical (TyrO(.)) with (.)NO(2) yields 45 +/- 3% 3-nitrotyrosine and that a major product of the reaction of TyrO(.) with (.)NO is 3,3'-dityrosine. Radiolysis was used to generate (.)NO and O-(2) in the presence of tyrosine and bicarbonate at pH 7.5 +/- 0.1. The nitration yield was found to be dose rate-dependent, and the yield per radical produced by pulse radiolysis was identical to that obtained with authentic peroxynitrite. The proposed mechanism that accounts for the data is as follows: (i) In the presence of CO(2) the reaction of (.)NO with O-(2) yields 33% (.)NO(2) and CO-(3), where the latter reacts rapidly with tyrosine to form TyrO(.); (ii) The formation of 3-nitrotyrosine takes place via the reaction of (.)NO(2) with TyrO(.), which is the main process at high dose rates; and (iii) Under continuous generation of (.)NO and O-(2), the formation of 3-nitrotyrosine is strongly suppressed because of efficient scavenging of (.)NO(2) by tyrosine. The proposed model shows that the highest nitration yield is obtained for similar fluxes of (.)NO and O-(2) and is completely inhibited upon excess production of O-(2) because of efficient scavenging of TyrO(.) by O-(2). The biological implications of these findings are discussed.
Goldstein
S
S
Department of Physical Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Czapski
G
G
Lind
J
J
Merényi
G
G
D000818:Animals; D005609:Free Radicals / Q000737:chemistry*; D006801:Humans; D009566:Nitrates / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry*
D005609:Free Radicals; D009566:Nitrates; C039642:peroxynitric acid; D014443:Tyrosine