Oxygen equilibrium of hemoglobin E

Bunn, H. Franklin; Meriwether, Wilhelm D.; Balcerzak, Stanley P.; Rucknagel, Donald L.

doi:10.1172/jci107125

Cited by 26 publications

(17 citation statements)

References 15 publications

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“…Oxygen Binding Properties-A limited series of oxygen affinity measurements conducted at high and low salt concentrations in phosphate buffer, pH 7.4, revealed the same minor differences in the P 50 and Hill coefficient between HbA and HbE as reported previously (19,20). Overall, the results are consistent with earlier reports that HbE oxygen binding is similar to HbA (19).…”

Section: Functional Studiessupporting

confidence: 89%

“…How does the HbE mutation contribute to the ␤ 0 -thalassemia-dependent spectrum of pathophysiologies in HbE disease? Oxygen binding properties of HbE appear to be similar to that of HbA; the HbE tetramer is reported to exhibit normal oxygen binding in the presence of phosphates and at physiological ionic strength (19) but with an increase in oxygen affinity under conditions of low salt concentration (20). Biochemical studies in vitro established a decreased stability of HbE attributed to the positively charged substitution at the site of mutation located near the ␣ 1 ␤ 1 interface (21)(22)(23)(24) that has yet to be linked to in vivo RBC alterations and pathophysiology (13).…”

mentioning

confidence: 89%

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Structural and Functional Studies Indicating Altered Redox Properties of Hemoglobin E

Roche

Malashkevich

Balazs

et al. 2011

Journal of Biological Chemistry

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Hemoglobin (Hb) E (␤-Glu26Lys) remains an enigma in terms of its contributions to red blood cell (RBC) pathophysiological mechanisms; for example, EE individuals exhibit a mild chronic anemia, and HbE/␤-thalassemia individuals show a range of clinical manifestations, including high morbidity and death, often resulting from cardiac dysfunction.The purpose of this study was to determine and evaluate structural and functional consequences of the HbE mutation that might account for the pathophysiology. Functional studies indicate minimal allosteric consequence to both oxygen and carbon monoxide binding properties of the ferrous derivatives of HbE. In contrast, redoxsensitive reactions are clearly impacted as seen in the following: 1) the ϳ2.5 times decrease in the rate at which HbE catalyzes nitrite reduction to nitric oxide (NO) relative to HbA, and 2) the accelerated rate of reduction of aquometHbE by L-cysteine (L-Cys). Sol-gel encapsulation studies imply a shift toward a higher redox potential for both the T and R HbE structures that can explain the origin of the reduced nitrite reductase activity of deoxyHbE and the accelerated rate of reduction of aquometHbE by cysteine. Deoxy-and CO HbE crystal structures (derived from crystals grown at or near physiological pH) show loss of hydrogen bonds in the microenvironment of ␤Lys-26 and no significant tertiary conformational perturbations at the allosteric transition sites in the R and T states. Together, these data suggest a model in which the HbE mutation, as a consequence of a relative change in redox properties, decreases the overall rate of Hb-mediated production of bioactive NO.

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Section: Functional Studiessupporting

confidence: 89%

mentioning

confidence: 89%

Structural and Functional Studies Indicating Altered Redox Properties of Hemoglobin E

Roche

Malashkevich

Balazs

et al. 2011

Journal of Biological Chemistry

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“…There is an apparent discrepancy between these results and the results published by Bunn working at a more physiological ionic strength [4]. The role of the saline environment is also confirmed by our normal results when working on intact cells or in the presence of 2,3 DPG.…”

Section: Resultscontrasting

confidence: 60%

Hemoglobin E: Its oxygen affinity in relation with the ionic environment

et al. 1974

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“…[12][13][14] In a single case of HbE ␤ thalassemia, the P 50 was remarkably elevated although the level of HbF in this patient, approximately 2%, was unusually low. 14 The present study shows that, overall, patients with HbE ␤ thalassemia are able to adapt to anemia by reducing the oxygen affinity of their red cells.…”

Section: Resultsmentioning

confidence: 71%

Adaptation to anemia in hemoglobin E-β thalassemia

Allen

Fisher

Premawardhena

et al. 2010

Blood

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Hemoglobin E ␤ thalassemia is the commonest form of severe thalassemia in many Asian countries. Its remarkably variable clinical phenotype presents a major challenge to determining its most appropriate management. In particular, it is not clear why some patients with this condition can develop and function well at very low hemoglobin levels. Here, we demonstrate that patients with hemoglobin E␤ thalassemia have a significant decrease in the oxygen affinity of their hemoglobin, that is an increased P 50 value, in response to anemia. This may in part reflect the lower level of hemoglobin F in this condition compared with other forms of ␤ thalassemia intermedia. The ability to rightshift the oxygen dissociation curve was retained across the spectrum of mild and severe phenotypes, despite the significantly higher levels of hemoglobin F in the former, suggesting that efforts directed at producing a modest increase in the level of hemoglobin F in symptomatic patients with this disease should be of therapeutic value. (Blood. 2010;116(24): 5368-5370)

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Oxygen equilibrium of hemoglobin E

Cited by 26 publications

References 15 publications

Structural and Functional Studies Indicating Altered Redox Properties of Hemoglobin E

Structural and Functional Studies Indicating Altered Redox Properties of Hemoglobin E

Hemoglobin E: Its oxygen affinity in relation with the ionic environment

Adaptation to anemia in hemoglobin E-β thalassemia

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