Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin

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dc.citation.firstpage265en_US
dc.citation.journalTitleFree Radical Biology and Medicineen_US
dc.citation.lastpage277en_US
dc.citation.volumeNumber69en_US
dc.contributor.authorMollan, Todd L.en_US
dc.contributor.authorJia, Yipingen_US
dc.contributor.authorBanerjee, Sambuddhaen_US
dc.contributor.authorWu, Gangen_US
dc.contributor.authorKreulen, R.Timothyen_US
dc.contributor.authorTsai, Ah-Limen_US
dc.contributor.authorOlson, John S.en_US
dc.contributor.authorCrumbliss, Alvin L.en_US
dc.contributor.authorAlayash, Abdu I.en_US
dc.date.accessioned2017-06-05T20:44:19Zen_US
dc.date.available2017-06-05T20:44:19Zen_US
dc.date.issued2014en_US
dc.description.abstractHaptoglobin (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.en_US
dc.identifier.citationMollan, Todd L., Jia, Yiping, Banerjee, Sambuddha, et al.. "Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin." <i>Free Radical Biology and Medicine,</i> 69, (2014) Elsevier: 265-277. https://doi.org/10.1016/j.freeradbiomed.2014.01.030.en_US
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2014.01.030en_US
dc.identifier.urihttps://hdl.handle.net/1911/94792en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordEPRen_US
dc.subject.keywordFerrylen_US
dc.subject.keywordHaptoglobinen_US
dc.subject.keywordHeme lossen_US
dc.subject.keywordHemoglobin Aen_US
dc.subject.keywordIron(IV) oxoen_US
dc.subject.keywordProtein-based radicalen_US
dc.subject.keywordRedox potentialen_US
dc.subject.keywordSpectroelectrochemistryen_US
dc.subject.keywordSulfhemoglobinen_US
dc.subject.keywordFree radicalsen_US
dc.titleRedox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobinen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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