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dc.contributor.authorMollan, Todd L.
Jia, Yiping
Banerjee, Sambuddha
Wu, Gang
Kreulen, R. Timothy
Tsai, Ah-Lim
Olson, John S.
Crumbliss, Alvin L.
Alayash, Abdu I.
dc.date.accessioned 2017-06-05T20:44:19Z
dc.date.available 2017-06-05T20:44:19Z
dc.date.issued 2014
dc.identifier.citation Mollan, Todd L., Jia, Yiping, Banerjee, Sambuddha, et al.. "Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin." Free Radical Biology and Medicine, 69, (2014) Elsevier: 265-277. https://doi.org/10.1016/j.freeradbiomed.2014.01.030.
dc.identifier.urihttps://hdl.handle.net/1911/94792
dc.description.abstract 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.
dc.language.iso eng
dc.publisher Elsevier
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.title Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin
dc.type Journal article
dc.citation.journalTitle Free Radical Biology and Medicine
dc.subject.keywordEPR
Ferryl
Haptoglobin
Heme loss
Hemoglobin A
Iron(IV) oxo
Protein-based radical
Redox potential
Spectroelectrochemistry
Sulfhemoglobin
Free radicals
dc.citation.volumeNumber 69
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2014.01.030
dc.identifier.pmcid PMC4104362
dc.identifier.pmid 24486321
dc.type.publication post-print
dc.citation.firstpage 265
dc.citation.lastpage 277


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