Abstract
Haptoglobin (Hp) sequesters hemoglobin (Hb) preventing the Hb-based damage occurring upon its physiological release into plasma. Here, reductive nitrosylation of ferric human hemoglobin [Hb(III)] bound to human haptoglobin (Hp) 1-1 and 2-2 [Hp1-1:Hb(III) and Hp2-2:Hb(III), respectively] has been investigated between pH 7.5 and 9.5, at T=20.0 °C. Over the whole pH range explored, only one process is detected reflecting NO binding to Hp1-1:Hb(III) and Hp2-2:Hb(III). Values of the pseudo-first-order rate constant for Hp1-1:Hb(III) and Hp2-2:Hb(III) nitrosylation (k) do not depend linearly on the ligand concentration but tend to level off. The conversion of Hp1-1:Hb(III)-NO to Hp1-1:Hb(II)-NO and of Hp2-2:Hb(III)-NO to Hp2-2:Hb(II)-NO is limited by the OH−- and H2O-based catalysis. In fact, bimolecular NO binding to Hp1-1:Hb(III), Hp2-2:Hb(III), Hp1-1:Hb(II), and Hp2-2:Hb(II) proceeds very rapidly. The analysis of data allowed to determine the values of the dissociation equilibrium constant for Hp1-1:Hb(III) and Hp2-2:Hb(III) nitrosylation [K = (1.2 ± 0.1) × 10−4 M], which is pH-independent, and of the first-order rate constant for Hp1-1:Hb(III) and Hp2-2:Hb(III) conversion to Hp1-1:Hb(II)-NO and Hp2-2:Hb(II)-NO, respectively (k′). From the dependence of k′ on [OH−], values of hOH– [(4.9 ± 0.6) × 103 M−1 s−1 and (6.79 ± 0.7) × 103 M−1 s−1, respectively] and of \( h_{{{\text{H}}_{ 2} {\text{O}}}} \) [(2.6 ± 0.3) × 10−3 s−1] were determined. Values of kinetic and thermodynamic parameters for Hp1-1:Hb(III) and Hp2-2:Hb(III) reductive nitrosylation match well with those of the Hb R-state, which is typical of the αβ dimers of Hb bound to Hp.
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Abbreviations
- CCP:
-
Complement control protein
- Hb:
-
Hemoglobin
- Hb(II):
-
Ferrous Hb
- Hb(III):
-
Ferric Hb
- Hb(II)-NO:
-
Nitrosylated Hb
- Hp:
-
Haptoglobin
- Hp1-1:
-
Phenotype 1-1 of Hp
- Hp2-2:
-
Phenotype 2-2 of Hp
- Hp1-1:Hb:
-
Hp1-1:Hb complex
- Hp1:Hb(II):
-
Hp1-1:Hb(II) complex
- Hp1-1:Hb(III):
-
Hp1-1:Hb(III) complex
- Hp1-1:Hb(II)-NO:
-
Hp1-1:Hb(II)-NO complex
- Hp2-2:Hb:
-
Hp2-2:Hb complex
- Hp2-2:Hb(II):
-
Hp2-2Hb(II) complex
- Hp2-2:Hb(III):
-
Hp2-2:Hb(III) complex
- Hp1-1:Hb(II)-NO:
-
Hp1-1:Hb(II)-NO complex
- Mb:
-
Myoglobin
- Mb(III):
-
Ferric Mb
- Ngb:
-
Neuroglobin
- SP-like domain:
-
Serine protease-like domain
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Acknowledgements
The grant of Excellence Departments, MIUR (Legge 232/2016, Articolo 1, Comma 314-337), is gratefully acknowledged.
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Ascenzi, P., De Simone, G., Polticelli, F. et al. Reductive nitrosylation of ferric human hemoglobin bound to human haptoglobin 1-1 and 2-2. J Biol Inorg Chem 23, 437–445 (2018). https://doi.org/10.1007/s00775-018-1551-y
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DOI: https://doi.org/10.1007/s00775-018-1551-y