Reverse Bohr effect on the oxygen-binding affinity of heme embedded in a bilayer of liposome as a hemoglobin model: pH-induced oxygen uptake and evolution by aqueous synthetic lipid-heme solution

1987 ◽  
pp. 1917 ◽  
Author(s):  
Makoto Yuasa ◽  
Yuichiroh Tani ◽  
Hiroyuki Nishide ◽  
Eishun Tsuchida
Keyword(s):  
Oxygen Uptake ◽  
Binding Affinity ◽  
Bohr Effect ◽  
Oxygen Binding

Influence of carbon monoxide on hemoglobin-oxygen binding

1976 ◽  
Vol 41 (6) ◽  
pp. 893-899 ◽  
Author(s):  
M. P. Hlastala ◽  
H. P. McKenna ◽  
R. L. Franada ◽  
J. C. Detter
Keyword(s):  
Carbon Monoxide ◽  
Oxygen Affinity ◽  
Co2 Concentration ◽  
Bohr Effect ◽  
Oxygen Binding ◽  
Dissociation Curve ◽  
Low Oxygen ◽  
Oxygen Dissociation ◽  
Initial Binding ◽  
Fixed Acid

The oxygen dissociation curve and Bohr effect were measured in normal whole blood as a function of carboxyhemoglobin concentration [HbCO]. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of isotonic NaOH or HCl at constant PCO2 (fixed acid Bohr effect). As [HbCO] varied through the range of 2, 25, 50, and 75%, P50 was 26.3, 18.0, 11.6, and 6.5 mmHg, respectively. CO2 Bohr effect was highest at low oxygen saturations. This effect did not change as [HbCO] was increased. However, as [HbCO] was increased from 2 to 75%, the fixed acid Bohr factor increased in magnitude from -0.20 to -0.80 at very low oxygen saturations. The effect of molecular CO2 binding (carbamino) on oxygen affinity was eliminated at high [HbCO]. These results are consistent with the initial binding of O2 or CO to thealpha-chain of hemoglobin. The results also suggest that heme-heme interaction is different for oxygen than for carbon monoxide.

scholarly journals Analysis of oxygen binding by hemoglobin on the basis of mean intrinsic thermodynamic quantities.

2006 ◽  
Vol 53 (3) ◽  
pp. 563-568 ◽  
Author(s):  
Abdol-Khalegh Bordbar ◽  
Sayed Habib-Allah Mousavi ◽  
Hamid Dazhampanah
Keyword(s):  
Binding Affinity ◽  
Compensation Effect ◽  
Cooperative Interaction ◽  
Thermodynamic Quantities ◽  
Oxygen Binding ◽  
Protein Species ◽  
Binding Data ◽  
Hoff Equation ◽  
Binding Curve ◽  
Partial Oxygen

The binding data for oxygenation of human hemoglobin, Hb, at various temperatures and in the absence and presence of 2,3-diphosphoglycerate, DPG, and inositol hexakis phosphate, IHP, were analyzed for extraction of mean intrinsic Gibbs free energy, DeltaGo, enthalpy, DeltaHo, and entropy, DeltaSo, of binding at various partial oxygen pressures. This method of analysis considers all the protein species present such as dimer and tetramer forms which were not considered by Imai et al. (Imai K et al., 1970, Biochim Biophys Acta 200: 189-196), in their analysis which was based on Adair equation. In this regard, the values of Hill equation parameters were estimated with high precision at all points of the binding curve and used for calculation of DeltaGo, DeltaHo and DeltaSo were also calculated by analysis of DeltaGo values at various temperatures using van't Hoff equation. The results represent the enthalpic nature of the cooperativity in Hb oxygenation and the compensation effect of intrinsic entropy. The interpretation of results also to be, into account the decrease of the binding affinity of sites for oxygen in the presence of DPG and IHP without any considerable changes in the site-site interaction (extent of cooperativity). In other words, the interactions between bound ligands, organic phosphates and oxygen, are more due to a decreasing binding affinity and not to the reduction of the cooperative interaction between sites. The results also document the more heterotropic effect of IHP compared to DPG.

scholarly journals Increased blood-oxygen binding affinity in Tibetan and Han Chinese residents at 4200 m

2014 ◽  
Vol 99 (12) ◽  
pp. 1624-1635 ◽  
Author(s):  
T. S. Simonson ◽  
G. Wei ◽  
H. E. Wagner ◽  
T. Wuren ◽  
A. Bui ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Han Chinese ◽  
Oxygen Binding ◽  
Blood Oxygen

scholarly journals LC-MS Analysis of Anti-Sickling Compounds in Cord Blood Derived RBCs Demonstrates Modification of Fetal Hemoglobin and Globin Chain Binding Preferences

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1074-1074
Author(s):  
Benjamin Vieira ◽  
Vu P. Hong ◽  
Kunal Desai ◽  
Martin K. Safo ◽  
David R. Light
Keyword(s):  
Cord Blood ◽  
Binding Affinity ◽  
Oxygen Affinity ◽  
Fetal Hemoglobin ◽  
Oxygen Binding ◽  
Globin Chain ◽  
Employment Equity ◽  
Globin Chains ◽  
N Terminus ◽  
Equity Ownership

Abstract Sickle cell disease (SCD) is a genetic hemoglobinopathy driven largely by a single codon mutation of the β-globin gene resulting in polymerization of hemoglobin S (HbS). Anti-sickling approaches that involve increasing the oxygen affinity of HbS to treat SCD are under development and offer the potential to directly prevent HbS polymerization and its downstream pathophysiology. Two such compounds, 5-hydroxymethylfurfural (5HMF) and voxelotor (GBT440) have entered clinical trials for SCD with promising results and exert their therapeutic effects by modifying the N-terminus of HbS α-globin chains to form a reversible Schiff base. Formation of this N-terminal adduct stabilizes the oxygen-bound R-state (in the R2 conformation) that increases the oxygen affinity of the altered HbS and delaying the polymerization of HbS. In addition, genetic and small molecule therapies designed to increase fetal hemoglobin (HbF) expression hold great potential for the treatment of SCD. Increasing the percentage of HbF in RBCs significantly slows sickling kinetics without affecting oxygen delivery. Combination approaches of high-O2-Hb modification with HbF inducing therapies clinically could result in increased efficacy in the treatment of SCD, but the impact of hemoglobin modifiers on fetal hemoglobin has not been reported. Our present studies investigated the effects of 5HMF and voxelotor in HbF-rich umbilical cord blood derived RBCs. HbF-rich (60-90%) RBCs were isolated from cord blood and incubated with commercially available 5HMF and voxelotor synthesized in-house. The effect of these compounds on hemoglobin oxygen affinity was determined by measuring the p50 of the oxygen saturation curve in whole cells. Sites of modification were determined directly by incubating compounds with the purified RBC lysate, stabilizing the N-terminal adduct by reduction to the amine, and analysis of the resulting modification by LC-MS. Similar to the reported p50 shifts with normal adult hemoglobin (HbA) and HbS, 5HMF and voxelotor increased the oxygen-binding affinity of HbF with an EC50 of 7.9 mM and 560 mM respectively. 1 mM voxelotor lowered cord RBC p50 to 4 mmHg in vitro. LC-MS analysis showed that 5HMF exclusively modified the N-terminus of the α-globin chain, with no modification of b-globin and g-globin chains. Unexpectedly, the α-globin, β-globin and γ-globin chains were all modified by voxelotor following incubation with cord blood. Voxelotor was also shown to modify both α-globin and the β-globin or βS-globin chains on purified HbA or HbS, respectively. These data contrast with published crystallography data demonstrating that voxelotor selectively modifies a single α-globin chain in CO-ligated HbS (Oksenberg et al 2016). Although anti-sickling aromatic aldehydes have similar effects on the oxygen binding affinity of HbA, HbS and HbF, they can vary in their selectivity for modification of the α-globin and beta-like chains of HbF, HbA, and HbS (Abraham et al. 1995). To further investigate our data with voxelotor and increase our understanding of this class of molecules, other hemoglobin modifying aldehyde molecules such as 5-formylsalicyclic acid (5FSA), tucaresol and velaresol (BW12C) will be examined. Disclosures Vieira: Bioverativ a Sanofi Company: Employment. Hong:Bioverativ a Sanofi Company: Employment, Equity Ownership. Desai:Bioverativ a Sanofi Company: Employment, Equity Ownership. Safo:Bioverativ a Sanofi Company: Consultancy; Virginia Commonwealth University: Employment. Light:Bioverativ a Sanofi Company: Employment, Equity Ownership.

Oxygen binding in alligator blood related to temperature, diving, and "alkaline tide"

1986 ◽  
Vol 251 (5) ◽  
pp. R901-R908 ◽  
Author(s):  
R. E. Weber ◽  
F. N. White
Keyword(s):  
Temperature Sensitivity ◽  
Bohr Effect ◽  
Alligator Mississippiensis ◽  
Breath Holding ◽  
Oxygen Binding ◽  
Constant Ph ◽  
The Face ◽  
High O2 ◽  
Alkaline Tide

Blood of Alligator mississippiensis has a relatively high O2 affinity, the half-saturation O2 tension (P50) = 24.5 Torr at pH 7.495, the arterial, normocapnic pH at 25 degrees C. Although the overall temperature sensitivity of P50 at 15, 25, and 35 degrees C and constant pH is low, the effect on P50 almost doubles when measured at the in vivo pH of each temperature (delta Happ = -24 and -47 kJ/mol, respectively). The CO2 Bohr effect (theta CO2 = -0.95) is 5.5 times greater than the fixed acid Bohr effect (theta FA), and the Haldane effect is small (approximately 0.03 pH units). The relatively high O2 affinity may ensure efficient utilization of the lung O2 reserve during breath holding and diving, whereas its pronounced in vivo temperature sensitivity may be adaptive to the high temperature quotients of the organismic O2 requirement. The large difference between theta CO2 and theta FA will favor constancy in blood O2 affinity in the face of large activity-induced increases in blood lactate and pronounced feeding-induced alkaloses. These "alkaline tides," which result from an exchange of plasma Cl- for HCO-3 across the gut wall, appear to be only slightly compensated by increased blood CO2 tensions. The results are additionally discussed in terms of allosteric modulation of hemoglobin-O2 affinity in crocodilians.

Oxygen binding and its allosteric control in hemoglobin of the pulmonate snail, Biomphalaria glabrata

1999 ◽  
Vol 276 (2) ◽  
pp. R347-R356 ◽  
Author(s):  
Jon Bugge ◽  
Roy E. Weber
Keyword(s):  
Equilibrium Constant ◽  
Divalent Cations ◽  
Biomphalaria Glabrata ◽  
Cation Binding ◽  
Bohr Effect ◽  
Independent Effect ◽  
Control Mechanisms ◽  
Oxygen Binding ◽  
Allosteric Control ◽  
Association Equilibrium

Pulmonate snails that experience extreme variations in gas tensions and temperatures possess extracellular, high-molecular mass (∼1.7 × 106 Da) hemoglobins (Hbs) that are little known as regards oxygenation and allosteric characteristics. Biomphalaria glabrata hemolymph exhibits a high O2 affinity (half-saturation O2 tension = 6.1 mmHg; pH 7.7, 25°C), pronounced Bohr effect (Bohr factor = −0.5), and pH-dependent cooperativity (Hill’s cooperativity coefficient at half-saturation = 1.1–2.0). Divalent cations increase O2 affinity, Ca2+ exerting greater effect than Mg2+. Analyses in terms of the Monod-Wyman-Changeux model indicate novel O2 affinity control mechanisms. In contrast to vertebrate Hb, where organic phosphates and protons lower affinity via decreased O2association equilibrium constant of Hb in low-affinity state ( K T), and to extracellular annelid Hbs, where protons and cations primarily modulate O2 association equilibrium constant of Hb in high-affinity state ( K R), in B. glabrata Hb, the Bohr effect is mediated predominantly via K R and the cation effect via K T, reflecting preferential, oxygenation-linked proton binding to oxygenated Hb and cation binding to deoxygenated Hb. CO2 has no specific (pH independent) effect. Nonlinear van’t Hoff plots show temperature dependence of the overall heats of oxygenation, indicating oxy-deoxy heat capacity differences. The findings are related to possible physiological significance in pond habitats.

scholarly journals Intraspecific variation and plasticity in mitochondrial oxygen binding affinity as a response to environmental temperature

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Dillon J. Chung ◽  
P. R. Morrison ◽  
H. J. Bryant ◽  
E. Jung ◽  
C. J. Brauner ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Intraspecific Variation ◽  
Environmental Temperature ◽  
Oxygen Binding
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