Bohr effect of human hemoglobin A: Magnitude of negative contributions determined by the equilibrium between two tertiary structures

Okonjo, Kehinde O.; Olatunde, Abimbola M.; Fodeke, Adedayo A.; Babalola, Jonathan O.

doi:10.1016/j.bpc.2014.04.002

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…Haemoglobin (Hb) is the most important erythrocyte protein, and structural variations in Hb affect the function of these cells as well as vasoconstriction capacity. Environmental changes, temperature increases, and pH deviations, together with chemical modifications, can induce structural and functional alterations in Hb 9 10 11 . Moreover, a disordered Hb conformation or Hb aggregation in erythrocytes, resulting from oxidative stress in diabetic patients, accelerates the development and progression of diabetes and its complications 12 13 14 .…”

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confidence: 99%

The impact of the HbA1c level of type 2 diabetics on the structure of haemoglobin

Ruan

Yong

et al. 2016

Sci Rep

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This study explores the impact of HbA1c levels on the structure of haemoglobin (Hb) in patients with type 2 diabetes. Seventy-four diabetic patients were classified into the following two groups based on their level of HbA1c: group A, patients with good glycaemic control (HbA1c < 7.0%, n = 36); group B, patients with persistent hyperglycaemia (HbA1c ≥ 9.0%, n = 38). Thirty-four healthy people served as controls (group H). Hb structure was examined by Fourier transform infrared spectroscopy (FTIR), and diabetic erythrocytes were modelled to estimate the impact of glucose on these cells and Hb. Increasing glucose concentrations altered both erythrocyte parameters and the Hb secondary structure. Group B differed significantly from group H (p < 0.05): in the former, the ordered Hb secondary structure had a strong tendency to transform into a disordered secondary structure, decreasing structural stability. We presumed here that high HbA1c levels might be a factor contributing to Hb structural modifications in diabetic patients. FTIR spectral analysis can provide a novel way to investigate the pathogenesis of type 2 diabetes mellitus.

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confidence: 99%

The impact of the HbA1c level of type 2 diabetics on the structure of haemoglobin

Ruan

Yong

et al. 2016

Sci Rep

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“…[1][2][3] Full conversion to the carbonmonoxy derivative was confirmed with previously obtained spectrum of carbonmonoxyhaemoglobin. 4 Conversion to aquomethaemoglobin was carried out by oxidation of oxyhaemoglobin with two-fold molar excess K 3 Fe(CN) 6 . Each derivative was passed through a Dintzis ion exchange column to remove the endogenous ions.…”

Section: Preparation Of Haemoglobinmentioning

confidence: 99%

“…The number and pK a of the ionizable groups linked to the pH dependence of the K EQ of the reaction of DTNB with the haemoglobin were analyzed based on previous findings that: (i) CysF9[93]â sulfhydryl group of liganded haemoglobin exist in two tertiary conformations; cis to the terminal amino group (r-conformation) and cis to the carbonyl group (t-conformation), [20][21] and (ii) that these two sulfhydryl conformations are coupled to transitions between the two tertiary structures in dynamic equilibrium. 4,22 In the experiment reported here, the reaction of DTNB with three derivatives of liganded stripped haemoglobin (haemoglobin that is free of organic phosphate) and three derivatives of inositol-P 6 bound haemoglobin were studied. Inositol-P 6 is known to favour T conformation.…”

Section: Fitting Of Experimental Data To Various Equilibria Steps In mentioning

confidence: 99%

“…Sulfhydryl groups at position F9[93]â is known to be reactive with both Boyer 's and Ellman's reagent in all mammalian and avian haemoglobins. [2][3][4]11,12,17,23,26,27 We therefore assigned the only pair of p-MB and DTNB reactive sulfhydryl group in the bat haemoglobin to position F9[93]â.…”

Section: Number Of Reactive Sulfhydryl Groupsmentioning

confidence: 99%

“…Transitions between r and t tertiary conformations are accompanied by change in the pK a s of ionization of the ionizable groups that are linked to the reaction of DTNB with the CysF9[93]â haemoglobin sulfhydryl group. 4 The affinity of human haemoglobin for oxygen has been shown to be regulated by the organic phosphate, 2,3-bisphosphoglycerate (2,3-BPG). 5-8 2,3-BPG is a small molecule with a high density of negative charge.…”

Section: Introductionmentioning

confidence: 99%

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Organic phosphate binding inhibits high pH t-isomerization of the ß-chain in straw-coloured fruit bat (Eidolon helvum) haemoglobin

Fodeke

2017

S.Afr.j.chem.

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Understanding the systematic structural changes accompanying allosteric effector binding to haemoglobin should provide some clues to the understanding of structure-function relationship in other multimeric enzymes. The affinities of the CysF9[93]â sulfhydryl group of oxy-, carbomonoxy-and aquomet-derivatives of straw-coloured fruit bat (Eidolon helvum) haemoglobin (SCFB-Hb) for 5,5'-dithiobis(2-nitrobenzoate) (DTNB) were measured in the range 5.6 £ pH £ 9.0 using stripped and inositol hexakisphosphate (inosito-P 6 ) bound haemoglobin. The data were analyzed on the basis of findings that the tertiary structure of the product of the reaction of DTNB with haemoglobin CysF9[93]â sulfhydryl group exists in two conformations; r and t. The result shows that the affinity of DTNB for SCFB-Hb in both r and t conformations are coupled to the ionizations of two ionizable groups, HisH21[143]â and HisFG4[97]â. In the r conformation, the presence of inositol-P 6 reduces the pK a of HisH21[143]â by 1.24 units and that of HisFG4[97]â by 2.74. In the t conformation, inositol-P 6 raises the pK a of HisH21[143]â by 1.10 pK a units whereas that of HisFG4[97]â was increased by 0.78 pK a units. Change in pK a of ionization of the ionizable groups and isomerization of the tertiary conformations are important modulators of organic phosphate binding. KEYWORDS Sulfhydryl group, inositol hexakisphosphate, ionizable group, stripped haemoglobin, r↔t isomerization, 5,5'-dithiobis(2nitrobenzoate).

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Bohr effect of native and chemically modified hemoglobins: Quantitative analyses based on the Wyman equation

Okonjo

2017

Biophysical Chemistry

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Bohr effect of human hemoglobin A: Magnitude of negative contributions determined by the equilibrium between two tertiary structures

Cited by 10 publications

References 30 publications

The impact of the HbA1c level of type 2 diabetics on the structure of haemoglobin

The impact of the HbA1c level of type 2 diabetics on the structure of haemoglobin

Organic phosphate binding inhibits high pH t-isomerization of the ß-chain in straw-coloured fruit bat (Eidolon helvum) haemoglobin

Bohr effect of native and chemically modified hemoglobins: Quantitative analyses based on the Wyman equation

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