Determination of interdependent ligand effects on human red cell oxygen affinity

1982 ◽  
Vol 42 (4) ◽  
pp. 339-345
Author(s):  
W. G. Zijlstra ◽  
B. Oeseburg ◽  
G. Kwant ◽  
A. Zwart
Keyword(s):  
Oxygen Affinity ◽  
Red Cell ◽  
Ligand Effects

Comparative evaluation of fifteen anti-sickling agents

Blood ◽  
1983 ◽  
Vol 61 (4) ◽  
pp. 693-704 ◽  
Author(s):  
H Chang ◽  
SM Ewert ◽  
RM Bookchin ◽  
RL Nagel
Keyword(s):  
Nitrogen Mustard ◽  
Potent Inhibitor ◽  
Oxygen Affinity ◽  
Red Cell ◽  
Red Cell Indices ◽  
Oxygen Affinity Of Hemoglobin ◽  
High Concentrations ◽  
Further Development

Abstract Fifteen compounds reported to be inhibitors of gelation or sickling were studied by standard methods. These tests included (1) the determination of the solubility of deoxyhemoglobin S or Csat, (2) evaluation of sickling in whole SS blood at various pO2s, (3) measurement of the oxygen affinity of hemoglobin and blood, and (4) examination of red cell indices and morphology. Among the 4 noncovalent agents tested, butylurea was the most potent inhibitor of gelation and sickling in vitro; however, relatively high concentrations were required compared to the covalent agents. In the latter group, bis-(3,5 dibromosalicyl)-fumarate, nitrogen mustard, and dimethyladipimidate were especially effective inhibitors of gelation and/or sickling. All of these compounds require further development before they can be considered for clinical use.

scholarly journals Comparative evaluation of fifteen anti-sickling agents

Blood ◽  
1983 ◽  
Vol 61 (4) ◽  
pp. 693-704
Author(s):  
H Chang ◽  
SM Ewert ◽  
RM Bookchin ◽  
RL Nagel
Keyword(s):  
Nitrogen Mustard ◽  
Potent Inhibitor ◽  
Oxygen Affinity ◽  
Red Cell ◽  
Red Cell Indices ◽  
Oxygen Affinity Of Hemoglobin ◽  
High Concentrations ◽  
Further Development

Fifteen compounds reported to be inhibitors of gelation or sickling were studied by standard methods. These tests included (1) the determination of the solubility of deoxyhemoglobin S or Csat, (2) evaluation of sickling in whole SS blood at various pO2s, (3) measurement of the oxygen affinity of hemoglobin and blood, and (4) examination of red cell indices and morphology. Among the 4 noncovalent agents tested, butylurea was the most potent inhibitor of gelation and sickling in vitro; however, relatively high concentrations were required compared to the covalent agents. In the latter group, bis-(3,5 dibromosalicyl)-fumarate, nitrogen mustard, and dimethyladipimidate were especially effective inhibitors of gelation and/or sickling. All of these compounds require further development before they can be considered for clinical use.

scholarly journals Crystallization and X-ray diffraction data analysis of human deoxyhaemoglobin A0 fully stripped of any anions

1999 ◽  
Vol 55 (11) ◽  
pp. 1914-1916 ◽  
Author(s):  
F. A. V. Seixas ◽  
W. F. de Azevedo ◽  
M. F. Colombo
Keyword(s):  
Diffraction Data ◽  
Oxygen Affinity ◽  
X Ray Diffraction ◽  
Structural Explanation ◽  
Human Haemoglobin ◽  
X Ray ◽  
High Resolution Structure ◽  
Allosteric Properties

In this work, initial crystallographic studies of human haemoglobin (Hb) crystallized in isoionic and oxygen-free PEG solution are presented. Under these conditions, functional measurements of the O2-linked binding of water molecules and release of protons have evidenced that Hb assumes an unforeseen new allosteric conformation. The determination of the high-resolution structure of the crystal of human deoxy-Hb fully stripped of anions may provide a structural explanation for the role of anions in the allosteric properties of Hb and, particularly, for the influence of chloride on the Bohr effect, the mechanism by which Hb oxygen affinity is regulated by pH. X-ray diffraction data were collected to 1.87 Å resolution using a synchrotron-radiation source. Crystals belong to the space group P21212 and preliminary analysis revealed the presence of one tetramer in the asymmetric unit. The structure is currently being refined using maximum-likelihood protocols.

Red cell oxygen affinity in fetal sheep: role of 2,3-DPG and adult hemoglobin

1978 ◽  
Vol 45 (1) ◽  
pp. 7-10 ◽  
Author(s):  
H. Bard ◽  
J. C. Fouron ◽  
J. E. Robillard ◽  
A. Cornet ◽  
M. A. Soukini
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Oxygen Affinity ◽  
Fetal Life ◽  
Red Cell ◽  
Adult Type ◽  
Fetal Sheep ◽  
Adult Hemoglobin ◽  
Relationship Of

Studies were carried out during fetal life in sheep to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the switchover to adult hemoglobin synthesis in regulating the position of the fetal red cell oxygen-affinity curve in utero. Adult hemoglobin first appeared near 120 days of gestation. The mean oxygen tension at which hemoglobin is half saturated (P50) prior to 120 days of gestation remained constant at 13.9 +/- 0.3 (SD) Torr and then increased gradually as gestation continued, reaching 19 Torr at term. During the interval of fetal life studied, the level of DPG was 4.43 +/- 1.63 (SD) micromol/g Hb and the deltapH between plasma and red blood cells was 0.227 +/- 0.038 (SD); neither was affected by gestational age. The decrease in the red cell oxygen affinity after 120 days of gestation ocrrelated with the amount of adult hemoglobin present in the fetus (r = 0.78; P less than 0.001). This decrease can be attributed only to the amount of the adult-type hemoglobin present, and not to DPG, or to changes in the deltapH between plasma and red blood cells, because both remained stable during the last trimester.

Response of breeding sows to long term dietary supplementation with folic acid

1994 ◽  
Vol 1994 ◽  
pp. 153-153
Author(s):  
P.B. Lynch ◽  
P.J.A. Sheehy
Keyword(s):  
Folic Acid ◽  
Dietary Supplementation ◽  
Red Cell ◽  
Restricted Feeding ◽  
Meat And Bone Meal ◽  
Bone Meal ◽  
Soyabean Meal ◽  
Dietary Treatments

Dietary supplementation with folic acid has been shown to improve reproductive performance in sows (Lindemann 1993). However most studies have been for one cycle only and few have examined the effect of supplementation over several parities.One hundred and thirty four crossbred sows ranging in parity from 2 to 4 were selected at farrowing and randomly allocated to two dietary treatments of low and high supplemental folic acid (0 and 10 g per tonne, Roche Products Ltd.). Treatments were applied for the following three lactations and post weaning periods, two full pregnancies and to day 30 of the pregnancy following the third lactation. The diet fed contained barley, wheat, soyabean meal and meat and bone meal with nutrient levels of 14.0 MJ DE/kg and 1.02% lysine. Sows were individually penned throughout with restricted feeding in pregnancy (2.2 kg/day increasing to 2.5 kg/day in the final month), and ad libitum in lactation (approx 5.0 kg/day) and post weaning (approx 3.4 kg/day). Blood samples for determination of plasma and red cell folate were taken from 14 sows per treatment on days 4, 50 and 110 of one cycle. These were determined by a microbiological assay (modification of methods of Scott et al 1974 and Wilson and Home 1982).

scholarly journals Effect of oxalate and malonate on red cell metabolism

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1389-1393
Author(s):  
E Beutler ◽  
L Forman ◽  
C West
Keyword(s):  
Pyruvate Kinase ◽  
Cell Metabolism ◽  
Inhibitory Effect ◽  
Red Cells ◽  
Red Cell ◽  
Acid Analogue ◽  
2,3 Dpg

The addition of oxalate to blood stored in Citrate-phosphate-dextrose (CPD) produces a marked improvement in 2,3-diphosphoglycerate (2,3-DPG) preservation; an increase in 2,3-DPG levels can also be documented in short-term incubation studies. Oxalate is a potent in vitro inhibitor of red cell lactate dehydrogenase, monophosphoglycerate mutase, and pyruvate kinase (PK). In the presence of fructose 1,6-diphosphate the latter inhibitory effect is competitive with phospho(enol)pyruvate (PEP). Determination of the levels of intermediate compounds in red cells incubated with oxalate suggest the presence of inhibition at the PK step, indicating that this is the site of oxalate action. Apparent inhibition at the glyceraldehyde phosphate dehydrogenase step is apparently due to an increase in the NADH/NAD ratio. Oxalate had no effect on the in vivo viability of rabbit red cells stored in CPD preservatives for 21 days. Greater understanding of the toxicity of oxalate is required before it can be considered suitable as a component of preservative media, but appreciation of the mechanism by which it affects 2,3-DPG levels may be important in design of other blood additives. Malonate, the 3-carbon dicarboxylic acid analogue of oxalate late did not inhibit pyruvate kinase nor affect 2,3-DPG levels.

scholarly journals Hemoglobin Non-equilibrium Oxygen Dissociation Curve

2020 ◽  
Author(s):  
Rosella Scrima ◽  
Sabino Fugetto ◽  
Nazzareno Capitanio ◽  
Domenico L. Gatti
Keyword(s):  
Partial Pressure ◽  
Correct Diagnosis ◽  
Oxygen Affinity ◽  
Oxygen Dissociation Curve ◽  
Dissociation Curve ◽  
High Affinity ◽  
Oxygen Dissociation ◽  
Sequential Binding ◽  
Non Equilibrium

AbstractAbnormal hemoglobins can have major consequences for tissue delivery of oxygen. Correct diagnosis of hemoglobinopathies with altered oxygen affinity requires a determination of hemoglobin oxygen dissociation curve (ODC), which relates the hemoglobin oxygen saturation to the partial pressure of oxygen in the blood. Determination of the ODC of human hemoglobin is typically carried out under conditions in which hemoglobin is in equilibrium with O2 at each partial pressure. However, in the human body due to the fast transit of RBCs through tissues hemoglobin oxygen exchanges occur under non-equilibrium conditions. We describe the determination of non-equilibrium ODC, and show that under these conditions Hb cooperativity has two apparent components in the Adair, Perutz, and MWC models of Hb. The first component, which we call sequential cooperativity, accounts for ∼70% of Hb cooperativity, and emerges from the constraint of sequential binding that is shared by the three models. The second component, which we call conformational cooperativity, accounts for ∼30% of Hb cooperativity, and is due either to a conformational equilibrium between low affinity and high affinity tetramers (as in the MWC model), or to a conformational change from low to high affinity once two of the tetramer sites are occupied (Perutz model).

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