scholarly journals Allosteric effectors do not alter the oxygen affinity of hemoglobin crystals

1997 ◽  
Vol 6 (2) ◽  
pp. 484-489 ◽  
Author(s):  
Andrea Mozzarelli ◽  
Claudio Rivetti ◽  
Gian Luigi Rossi ◽  
William A. Eaton ◽  
Eric R. Henry
Keyword(s):  
Oxygen Affinity ◽  
Allosteric Effectors ◽  
Oxygen Affinity Of Hemoglobin

A Comparison of Diphosphonoglyceric Acid and Diphosphoglyceric Acid as Allosteric Effectors for Hemoglobin

1973 ◽  
Vol 51 (7) ◽  
pp. 1120-1122 ◽  
Author(s):  
Ruth E. Benesch ◽  
Reinhold Benesch ◽  
Suzanna Yung ◽  
Erich Baer ◽  
Ranga Robinson
Keyword(s):  
Binding Site ◽  
Oxygen Affinity ◽  
Glyceric Acid ◽  
Oxygen Release ◽  
Allosteric Effectors ◽  
Oxygen Affinity Of Hemoglobin

2,3-Diphosphoglycerate is the major intraerythrocytic cofactor for oxygen release by hemoglobin. The phosphono analogue, 2,3-diphosphono-DL-glyceric acid, has only minimal effects on the oxygen affinity of hemoglobin. This finding is readily understood in terms of the electrostatic and spatial requirements of the binding site in deoxyhemoglobin.

scholarly journals GBT1118, a compound that increases the oxygen affinity of hemoglobin, improves survival in murine hypoxic acute lung injury

2018 ◽  
Vol 124 (4) ◽  
pp. 899-905 ◽  
Author(s):  
Nathan D. Putz ◽  
Ciara M. Shaver ◽  
Kobina Dufu ◽  
Chien-Ming Li ◽  
Qing Xu ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Oxygen Affinity ◽  
High Dose ◽  
Novel Therapy ◽  
Oxygen Affinity Of Hemoglobin

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and pulmonary edema, leading to arterial hypoxemia and death if the hypoxemia is severe. Strategies to correct hypoxemia have the potential to improve clinical outcomes in ARDS. The goal of this study was to evaluate the potential of hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. The therapeutic effect of two different doses of GBT1118, a compound that increases the oxygen affinity of hemoglobin, was evaluated in a murine model of acute lung injury induced by intratracheal LPS instillation 24 h before exposure to 5% or 10% hypoxia ( n = 8–15 per group). As expected, administration of GBT1118 to mice significantly increased the oxygen affinity of hemoglobin. Compared with mice receiving vehicle control, mice treated with GBT1118 had significantly lower mortality after LPS + 5% hypoxia (47% with vehicle vs. 22% with low-dose GBT1118, 13% with high-dose GBT1118, P = 0.032 by log rank) and had reduced severity of illness. Mice treated with GBT1118 showed a sustained significant increase in SpO2 over 4 h of hypoxia exposure. Treatment with GBT1118 did not alter alveolar-capillary permeability, bronchoalveolar lavage (BAL) inflammatory cell counts, or BAL concentrations of IL-1β, TNF-α, or macrophage inflammatory protein-1α. High-dose GBT1118 did not affect histological lung injury but did decrease tissue hypoxia as measured intensity of pimonidazole (Hypoxyprobe) staining in liver ( P = 0.043) and kidney ( P = 0.043). We concluded that increasing the oxygen affinity of hemoglobin using GBT1118 may be a novel therapy for treating hypoxemia associated with acute lung injury. NEW & NOTEWORTHY In this study, we show that GBT1118, a compound that increases hemoglobin affinity for oxygen, improves survival and oxygen saturation in a two-hit lung injury model of intratracheal LPS without causing tissue hypoxia. Modulation of hemoglobin oxygen affinity represents a novel therapeutic approach to treatment of acute lung injury and acute respiratory distress syndrome, conditions characterized by hypoxemia.

NTP pattern of avian embryonic red cells: role of RNA degradation and AMP deaminase/5′-nucleotidase activity

2003 ◽  
Vol 284 (3) ◽  
pp. R771-R779 ◽  
Author(s):  
Rosemarie Baumann ◽  
Robert Götz ◽  
Stefanie Dragon
Keyword(s):  
Hormonal Regulation ◽  
Oxygen Affinity ◽  
Erythroid Differentiation ◽  
Rna Degradation ◽  
Amp Deaminase ◽  
Key Enzymes ◽  
Allosteric Effectors ◽  
Hemoglobin Oxygen Affinity ◽  
Adult Hemoglobin

During terminal erythroid differentiation, degradation of RNA is a potential source for nucleotide triphosphates (NTPs) that act as allosteric effectors of hemoglobin. In this investigation, we assessed the developmental profile of RNA and purine/pyrimidine trinucleotides in circulating embryonic chick red blood cells (RBC). Extensive changes of the NTP pattern are observed which differ significantly from what is observed for adult RBC. The biochemical mechanisms have not been identified yet. Therefore, we studied the role of AMP deaminase and IMP/GMP 5′-nucleotidase, which are key enzymes for the regulation of the purine nucleotide pool. Finally, we tested the effect of major NTPs on the oxygen affinity of embryonic/adult hemoglobin. The results are as follows. 1) Together with ATP, UTP and CTP serve as allosteric effectors of hemoglobin. 2) Degradation of erythroid RNA is apparently a major source for NTPs. 3) Developmental changes of nucleotide content depend on the activities of key enzymes (AMP deaminase, IMP/GMP 5′-nucleotidase, and pyrimidine 5′-nucleotidase). 4) Oxygen-dependent hormonal regulation of AMP deaminase adjusts the red cell ATP concentration and therefore the hemoglobin oxygen affinity.

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