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

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dc.citation.firstpage265
dc.citation.journalTitleFree Radical Biology and Medicine
dc.citation.lastpage277
dc.citation.volumeNumber69
dc.contributor.authorMollan, Todd L.
dc.contributor.authorJia, Yiping
dc.contributor.authorBanerjee, Sambuddha
dc.contributor.authorWu, Gang
dc.contributor.authorKreulen, R.Timothy
dc.contributor.authorTsai, Ah-Lim
dc.contributor.authorOlson, John S.
dc.contributor.authorCrumbliss, Alvin L.
dc.contributor.authorAlayash, Abdu I.
dc.date.accessioned2017-06-05T20:44:19Z
dc.date.available2017-06-05T20:44:19Z
dc.date.issued2014
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.
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.
dc.identifier.doihttps://doi.org/10.1016/j.freeradbiomed.2014.01.030
dc.identifier.urihttps://hdl.handle.net/1911/94792
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.subject.keywordEPR
dc.subject.keywordFerryl
dc.subject.keywordHaptoglobin
dc.subject.keywordHeme loss
dc.subject.keywordHemoglobin A
dc.subject.keywordIron(IV) oxo
dc.subject.keywordProtein-based radical
dc.subject.keywordRedox potential
dc.subject.keywordSpectroelectrochemistry
dc.subject.keywordSulfhemoglobin
dc.subject.keywordFree radicals
dc.titleRedox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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