Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin
Open accessAbstract
Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation after hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally nonequivalent. We have investigated the functional and redox properties of Hb-Hp complexes prepared using commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of ~0.9 μM(-1) s(-1), irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO2 autoxidation by dissociating Hb tetramers into dimers, the rate observed for these bound dimers is three- to fourfold slower than that of Hb dimers free in solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below detectable levels. Intrinsic redox potentials (E1/2) of the ferric/ferrous pair of each Hb-Hp complex are similar, varying from +54 to +59 mV (vs NHE), and are essentially the same as reported by us previously for Hb-Hp complexes prepared from unfractionated Hp. All Hb-Hp complexes generate similar high amounts of ferryl Hb after exposure to hydrogen peroxide. Electron paramagnetic resonance data indicate that the yields of protein-based radicals during this process are approximately 4 to 5% and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions examined are equivalent to one another with respect to Hb binding and associated stability and redox properties and that this result should be taken into account in the design of phenotype-specific Hp therapeutics aimed at countering Hb-mediated vascular disease.
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The interplay between molten globules and heme disassociation defines human hemoglobin disassemblyPreprint
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Protein dynamics govern the oxyferrous state lifetime of an artificial oxygen transport protein
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The study of the quenching mechanism of hemoglobin by curcumin in nanoemulsion
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- Authors
- Mollan, T. L., Jia, Y., Banerjee, S., Wu, G., Timothy Kreulen, R., Tsai, A.-L., Olson, J. S., Crumbliss, A. L., & Alayash, A. I.
- Affiliations
- Center for Biologics Evaluation and Research (US)
- Duke University (US)
- Rice University (US)
- Corresponding author
- Alayash, Abdu I.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 69
- Pages
- 265-277
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC4104362
- OpenAlex
- W2065179469
- Cited by
- 62
- References
- 80
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 4 · 2014: 2
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rice Research Repository (Rice University) (acceptedVersion)
- Rice Research Repository (Rice University) (submittedVersion)
- Funders
- National Institutes of Health (HL110900 (A.I.A., J.S.O.), HL095820 (A.-L.T.))
- National Science Foundation (CHE 0809466 (A.L.C.))
- Duke University
- Welch Foundation (C-0612 (J.S.O.))
- U.S. Food and Drug Administration (MODSCI 2012)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Keywords
- haptoglobin, hemoglobin, heme oxygenation, heme loss, ferryl hemoglobin, redox potential, haptoglobin phenotypes, hydrogen peroxide, protein radicals, hemoglobin clearance, hemolysis
- MeSH terms
- Electron Spin Resonance Spectroscopy, Haptoglobins, Hemoglobins, Humans, Hydrogen Peroxide, Kinetics, Oxidation-Reduction, Phenotype, Polymers, Dimerization, Multiprotein Complexes
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