Haptoglobin (Hp) reacts with dimeric hemoglobin (Hb), shifts the equilibrium in favor of the αβ dimer and displays heme-based catalysis. Here, kinetics of peroxynitrite scavenging by ferric human haptoglobin1-1:hemoglobin and haptoglobin2-2:hemoglobin complexes (Hp1-1:Hb(III) and Hp2-2:Hb(III), respectively) is reported between pH 6.2 and 8.3 at 20.0 °C. The reactivity of Hp1-1:Hb(III) and Hp2-2:Hb(III) against peroxynitrite is similar to that of tetrameric Hb(III), reflecting the R-like structure of the αβ dimers of Hb(III) bound to Hp. To investigate the protective role of Hp1-1:Hb(III) and Hp2-2:Hb(III) against peroxynitrite-mediated nitration, the relative yield of nitro-l-tyrosine formed by the reaction of peroxynitrite with free l-tyrosine was determined. Interestingly, both Hp1-1:Hb(III) and Hp2-2:Hb(III) impair peroxynitrite-mediated nitration of free l-tyrosine. Therefore, Hp:Hb complexes could participate to the detoxification of reactive nitrogen and oxygen species in vivo, contributing to prevent extra-erythrocytic Hb-induced damage during hemolytic crisis.
Ascenzi, P., Coletta, M. (2018). Peroxynitrite Detoxification by Human Haptoglobin:Hemoglobin Complexes: A Comparative Study. THE JOURNAL OF PHYSICAL CHEMISTRY. B, 122(49), 11100-11107 [10.1021/acs.jpcb.8b05340].
Peroxynitrite Detoxification by Human Haptoglobin:Hemoglobin Complexes: A Comparative Study
Coletta M.
2018-01-01
Abstract
Haptoglobin (Hp) reacts with dimeric hemoglobin (Hb), shifts the equilibrium in favor of the αβ dimer and displays heme-based catalysis. Here, kinetics of peroxynitrite scavenging by ferric human haptoglobin1-1:hemoglobin and haptoglobin2-2:hemoglobin complexes (Hp1-1:Hb(III) and Hp2-2:Hb(III), respectively) is reported between pH 6.2 and 8.3 at 20.0 °C. The reactivity of Hp1-1:Hb(III) and Hp2-2:Hb(III) against peroxynitrite is similar to that of tetrameric Hb(III), reflecting the R-like structure of the αβ dimers of Hb(III) bound to Hp. To investigate the protective role of Hp1-1:Hb(III) and Hp2-2:Hb(III) against peroxynitrite-mediated nitration, the relative yield of nitro-l-tyrosine formed by the reaction of peroxynitrite with free l-tyrosine was determined. Interestingly, both Hp1-1:Hb(III) and Hp2-2:Hb(III) impair peroxynitrite-mediated nitration of free l-tyrosine. Therefore, Hp:Hb complexes could participate to the detoxification of reactive nitrogen and oxygen species in vivo, contributing to prevent extra-erythrocytic Hb-induced damage during hemolytic crisis.File | Dimensione | Formato | |
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