Copper and the oxidation of hemoglobin: a comparison of horse and human hemoglobins.
Abstract: Oxidation studies of hemoglobin by Cu(II) indicate that for horse hemoglobin, up to a Cu(II)/heme molar ratio of 0.5, all of the Cu(II) added is used to rapidly oxidize the heme. On the other hand, most of the Cu(II) added to human hemoglobin at low Cu(II)/heme molar ratios is unable to oxidize the heme. Only at Cu(II)/heme molar ratios greater than 0.5 does the amount of oxidation per added Cu(II) approach that of horse hemoglobin. At the same time, binding studies indicate that human hemoglobin has an additional binding site involving one copper for every two hemes, which has a higher copper affinity than the single horse hemoglobin binding site. The Cu(II) oxidation of human hemoglobin is explained utilizing this additional binding site by a mechanism where a transfer of electrons cannot occur between the heme and the Cu(II) bound to the high affinity human binding site. The electron transfer must involve the Cu(II) bound to the lower affinity human hemoglobin binding site, which is similar to the only horse hemoglobin site. The involvement of beta-2 histidine in the binding of this additional copper is indicated by a comparison of the amino acid sequences of various hemoglobins which possess the additional site, with the amino acid sequences of hemoglobins which do not possess the additional site. Zn(II), Hg(II), and N-ethylmaleimide (NEM) are found to decrease the Cu(II) oxidation of hemoglobin. The sulfhydryl reagents, Hg(II) and NEM, produce a very dramatic decrease in the rate of oxidation, which can only be explained by an effect on the rate for the actual transfer of electrons between the Cu(II) and the Fe(II). The effect of Zn(II) is much smaller and can, for the most part, be explained by the increased oxygen affinity, which affects the ligand dissociation process that must precede the electron transfer process.
Publication Date: 1976-11-30 PubMed ID: 187214DOI: 10.1021/bi00669a021Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This research article investigates the oxidation of hemoglobin, a protein in red blood cells, by copper ions (Cu(II)), comparing the behavior between horse and human hemoglobins. The study discovers that the rate of oxidation and binding sites of copper in both hemoglobin species are different, and impacts from certain chemical substances are also examined.
Comparative study of horse and human hemoglobins
- The investigation focuses on how the addition of copper ions (Cu(II)) affects the oxidation of hemoglobin in horses and humans.
- The study found that for horse hemoglobin, all of the Cu(II) added can rapidly oxidize the heme up to a Cu(II)/heme molar ratio of 0.5.
- Conversely, for human hemoglobin, most of the added Cu(II) cannot oxidize the heme at low Cu(II)/heme molar ratios. It is only when this ratio exceeds 0.5, that the oxidation rate approaches that of horse hemoglobin.
Discovery of an additional binding site in human hemoglobin
- Human hemoglobin further differentiates from horse hemoglobin as it has an additional binding site for copper. One copper ion can bind to every two hemes, and this binding site has a higher copper affinity than the single binding site in horse hemoglobin.
- This additional binding site in human hemoglobin is closely related with oxidation process; the electron transfer for oxidation can only occurs at the lower affinity human hemoglobin site (similar to the horse’s) instead of at this additional high-affinity site.
- The involvement of the amino acid, beta-2 histidine, in this binding site is suggested as hemoglobins with this additional site, were found to possess this amino acid.
The effect of chemical substances on hemoglobin oxidation
- The research also investigates how the chemical substances Zn(II), Hg(II), and N-ethylmaleimide (NEM) affect hemoglobin oxidation.
- The sulfhydryl reagents, Hg(II) and NEM, notably decreased the rate of oxidation, likely impacting the electron transfer between Cu(II) and the Iron(II) in hemoglobin.
- Zn(II) had a lesser impact on the oxidation process, with its effect mostly related to its increased oxygen affinity and subsequent influence on the ligand dissociation process necessary for electron transfer.
Cite This Article
APA
Rifkind JM, Lauer LD, Chiang SC, Li NC.
(1976).
Copper and the oxidation of hemoglobin: a comparison of horse and human hemoglobins.
Biochemistry, 15(24), 5337-5343.
https://doi.org/10.1021/bi00669a021 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Binding Sites
- Carbon Monoxide / pharmacology
- Cattle
- Copper / metabolism
- Electron Spin Resonance Spectroscopy
- Ethylmaleimide / pharmacology
- Heme / analysis
- Hemoglobins / metabolism
- Horses / blood
- Humans
- Kinetics
- Mercury / pharmacology
- Oxidation-Reduction
- Oxygen Consumption
- Rabbits
- Sheep
- Zinc / pharmacology
Citations
This article has been cited 1 times.- Van Dyke BR, Bakan DA, Glover KA, Hegenauer JC, Saltman P, Springer BA, Sligar SG. Site-directed mutagenesis of histidine residues involved in Cu(II) binding and reduction by sperm whale myoglobin. Proc Natl Acad Sci U S A 1992 Sep 1;89(17):8016-9.
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