Dissection of the radical reactions linked to fetal hemoglobin reveals enhanced pseudoperoxidase activity

Frontiers in Physiology
Khuanpiroon RatanasopaLeif Bulow

Abstract

In the presence of excess hydrogen peroxide (H2O2), ferrous (Fe(+2)) human hemoglobin (Hb) (α2β2) undergoes a rapid conversion to a higher oxidation ferryl state (Fe(+4)) which rapidly autoreduces back to the ferric form (Fe(+3)) as H2O2 is consumed in the reaction. In the presence of additional H2O2 the ferric state can form both ferryl Hb and an associated protein radical in a pseudoperoxidative cycle that results in the loss of radicals and heme degradation. We examined whether adult HbA (β2α2) exhibits a different pseudoenzymatic activity than fetal Hb (γ2α2) due to the switch of γ to β subunits. Rapid mixing of the ferric forms of both proteins with excess H2O2 resulted in biphasic kinetic time courses that can be assigned to γ/β and α, respectively. Although there was a 1.5 fold increase in the fast reacting γ /β subunits the slower reacting phases (attributed to α subunits of both proteins) were essentially the same. However, the rate constant for the auto-reduction of ferryl back to ferric for both proteins was found to be 76% higher for HbF than HbA and in the presence of the mild reducing agent, ascorbate there was a 3-fold higher reduction rate in ferryl HbF as opposed to ferryl HbA. Using quantitative mass spectrome...Continue Reading

References

Jan 2, 1976·European Journal of Biochemistry·M R EgmondP M Fasella
May 5, 1977·Journal of Molecular Biology·J A Frier, M F Perutz
Feb 27, 1992·Nature·C C MoserP L Dutton
Sep 1, 1988·Journal of Biochemical and Biophysical Methods·S M Snell, M A Marini
Jan 1, 1994·Free Radical Biology & Medicine·C GiuliviK J Davies
Apr 1, 1996·The Biochemical Journal·O Hofmann, T Brittain
Jul 21, 1998·Annals of the New York Academy of Sciences·B G Forget
Dec 16, 1998·Trends in Biochemical Sciences·J Stubbe, P Riggs-Gelasco
Nov 25, 2003·Analytical Chemistry·Alexey I NesvizhskiiRuedi Aebersold
Mar 27, 2004·Nature Reviews. Drug Discovery·Abdu I Alayash
Nov 9, 2005·Free Radical Biology & Medicine·Robert M JohnsonYe-Shih Ho
Dec 21, 2006·The Journal of Biological Chemistry·Yiping JiaAbdu I Alayash
Jan 16, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Malin KvistLeif Bülow
Jan 22, 2008·The Journal of Biological Chemistry·Agnes KeszlerNeil Hogg
Jan 25, 2008·Free Radical Biology & Medicine·Brandon J ReederMichael T Wilson
Apr 2, 2008·IUBMB Life·Laura Manca, Bruno Masala
Aug 30, 2008·The Journal of Biological Chemistry·Brandon J ReederMichael T Wilson
Oct 29, 2008·Evidence-based Complementary and Alternative Medicine : ECAM·Nicoletta BianchiRoberto Gambari
Nov 26, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Arlin B BloodGordon G Power
Aug 26, 2009·Antioxidants & Redox Signaling·Corinne C WidmerDominik J Schaer
Feb 23, 2010·Antioxidants & Redox Signaling·Brandon J Reeder
Apr 15, 2011·Blood·Idowu AkinsheyeMartin H Steinberg
Apr 28, 2011·American Journal of Hematology·Jeffrey LebensburgerLee M Hilliard
Dec 27, 2011·Placenta·U D AndersonS R Hansson
Jan 21, 2012·Blood Cells, Molecules & Diseases·Angela RissoGuglielmo Antonutto
Mar 19, 2014·Trends in Biotechnology·Abdu I Alayash

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Citations

Feb 22, 2017·Redox Biology·Sandeep ChakaneLeif Bulow
Feb 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Denisa HathaziRadu Silaghi-Dumitrescu
Jul 26, 2017·Proceedings of the National Academy of Sciences of the United States of America·Nils SchuthMichael Haumann
Feb 7, 2021·The British Journal of Ophthalmology·William HellströmAnn Hellström
Jun 22, 2021·International Journal of Biological Macromolecules·Selvaraju KanagarajanLi-Hua Zhu
Aug 16, 2017·Chemical Research in Toxicology·Xinmei DongDavid E Thompson

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