OXYGEN-BINDING AFFINITY OF LIPOSOMAL HEME UNDER SEMI PHYSIOLOGICAL CONDITIONS

1983 ◽  
Vol 12 (4) ◽  
pp. 473-476 ◽  
Author(s):  
Eishun Tsuchida ◽  
Hiroyuki Nishide ◽  
Makoto Yuasa ◽  
Mikiya Sekine
Keyword(s):  
Binding Affinity ◽  
Oxygen Binding ◽  
Physiological Conditions

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.

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

scholarly journals Dynamics of camel and human hemoglobin revealed by molecular simulations

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Amanat Ali ◽  
Soja Saghar Soman ◽  
Ranjit Vijayan
Keyword(s):  
Physiological Stress ◽  
Experimental Studies ◽  
Oxygen Binding ◽  
Human Hemoglobin ◽  
Heme Group ◽  
Structural Variations ◽  
Physiological Conditions ◽  
Cofactor Binding ◽  
Dynamics Simulations ◽  
T State

AbstractHemoglobin is one of the most widely studied proteins genetically, biochemically, and structurally. It is an oxygen carrying tetrameric protein that imparts the characteristic red color to blood. Each chain of hemoglobin harbors a heme group embedded in a hydrophobic pocket. Several studies have investigated structural variations present in mammalian hemoglobin and their functional implications. However, camel hemoglobin has not been thoroughly explored, especially from a structural perspective. Importantly, very little is known about how the heme group interacts with hemoglobin under varying conditions of osmolarity and temperature. Several experimental studies have indicated that the tense (T) state is more stable than the relaxed (R) state of hemoglobin under normal physiological conditions. Despite the fact that R state is less stable than the T state, no extensive structural dynamics studies have been performed to investigate global quaternary transitions of R state hemoglobin under normal physiological conditions. To evaluate this, several 500 ns all-atom molecular dynamics simulations were performed to get a deeper understanding of how camel hemoglobin behaves under stress, which it is normally exposed to, when compared to human hemoglobin. Notably, camel hemoglobin was more stable under physiological stress when compared to human hemoglobin. Additionally, when compared to camel hemoglobin, cofactor-binding regions of hemoglobin also exhibited more fluctuations in human hemoglobin under the conditions studied. Several differences were observed between the residues of camel and human hemoglobin that interacted with heme. Importantly, distal residues His58 of α hemoglobin and His63 of β hemoglobin formed more sustained interactions, especially at higher temperatures, in camel hemoglobin. These residues are important for oxygen binding to hemoglobin. Thus, this work provides insights into how camel and human hemoglobin differ in their interactions under stress.

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