Considerations for the Design of useful Synthetic Oxygen Carriers

Traylor, T. G.; Traylor, Patricia S.

doi:10.1146/annurev.bb.11.060182.000541

Cited by 54 publications

(20 citation statements)

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“…This crystal lattice is available to a wide pH range and various oxidation and ligation states [40] and therefore it allows the correlation of structural and functional differences. The existence of an acid Bohr effect in Dd Hb [34] might be anticipated from former binding studies of azide to aquomethaemoglobin [37]. Here we report on the pH dependence of O2 affinity of D. dendriticum haemoglobin.…”

supporting

confidence: 52%

Acid Bohr effect of a monomeric haemoglobin from Dicrocoelium dendriticum

Smit

Sick

Peterhans

et al. 1986

European Journal of Biochemistry

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The dioxygen affinity of Dicrocoelium dendriticum haemoglobin was determined as a function of pH with a thin-layer diffusion technique. From the oxygen dissociation and association curves Hill coefficients h equal 1 were obtained throughout. Ultracentrifugation studies prove this haemoglobin to be monomeric irrespective of pH and ligation state. Thus, Dicrocoelium haemoglobin is a non-cooperative monomer. It has the highest 0, affinity so far known for any monomeric haemoglobin : its half-saturation pressure, p s o value, ranges at 25°C from 0.016 mm Hg to 0.15 mm Hg (2.13-20.0 Pa) dependent on pH. Dicrocoelium haemoglobin shows an acid Bohr effect only and as such it constitutes a new class of haemoglobins. Its log p s o versus pH plot (Bohr effect curve) is characterized by a large amplitude, dlog p50 = 0.96, and an inflection point (Bohr effect pK) at pH 5.0. A model for the acid Bohr effect of D. dendriticum haemoglobin is proposed. By generalization, both the alkaline and the acid Bohr effect in various monomeric haemoglobins may arise from a single Bohr group complex (salt bridge). The interaction between ligand-binding sites in a single oligomeric molecule gives rise to cooperativity and nonhyperbolic ligand-binding curves [5]. In the absence of cooperativity the Hill coefficient h = 1. It may rise to the number of binding sites per molecule [6]. The mechanism of homotropic or haem -haem interaction in mammalian haemoglobins has been thoroughly investigated by X-ray analysis. Tetrameric haemoglobin molecules can switch between the quaternary structures T and R, with low and high ligand affinity respectively [7 -91. These differences in affinity must reside in the underlying tertiary conformations t and r of the individual subunits [lo, 111. Such conformational changes of the tertiary structure have been demonstrated in certain monomeric haemoglobins [12].The degree of polymerization differs for some haemoglobins depending on the state of ligation. The highest aggreDedicated to Professor C. Martius on the occasion of his 80th birthday.Correspondence to J. D. G. Smit gation state seems always associated with the unliganded protein. This ligand-linked aggregation can be considered as a special type of homotropic interaction because it leads also to h values greater then 1 [6]. In contrast, however, ligand affinity and protein concentration are interdependent if ligand-induced polymerization occurs. The phenomenon was first described for Petromyzon haemoglobin [13] but turns out to be quite common in haemoglobins of lower animals.Heterotropic interactions describe the influence of an effector on the affinity of a primary ligand. This type of regulation is common in haemoglobins, less so in haemocyanins and virtually unknown in haemerythrins [ 141. Many biological compounds modify the ligand affinity and homotropic interactions of haemoglobins. Amongst them are both anions and cations of salts [15] and organic phosphates like 2,3-bisphosphoglycerate in mammals, inositol pcntakisphosphate in birds, and ATP a...

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supporting

confidence: 52%

Acid Bohr effect of a monomeric haemoglobin from Dicrocoelium dendriticum

Smit

Sick

Peterhans

et al. 1986

European Journal of Biochemistry

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“…Although many studies of anaerobic redox reactions have shown that Hbs stabilized in high-O 2 -affinity R-state conformations are typically more readily oxidized than T-state stabilized forms, the structural differences which affect heme oxygenation do not show a uniform correlation with alterations in heme redox potential (22,24,33,34,47,72,83,99,111,118). Notably, as shown in Figures 3 and 4, IHP has a much more pronounced effect on the initial stages of Hb oxygenation than on oxidation (41).…”

Section: Allosteric Controls Of the Oxygenation And Redox Reactions Omentioning

confidence: 99%

Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

Bonaventura

Henkens

Alayash

et al. 2013

Antioxidants & Redox Signaling

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Significance: The broad classes of O 2 -binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O 2 -binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hbmediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298-2313. General PrinciplesEmergence of proteins capable of transporting O 2 I n this review, we examine the adaptive changes in the molecular controls of hemoglobin (Hb) oxygenation and oxidation that have evolved to meet the highly varied physiological and environmental demands of respiring organisms. Globins came into being during the planet's long early period of anoxia/hypoxia, and recent studies show that globins are either expressed or inducible in almost all cells (98). Studies have shown that one evolutionary pathway of Hb is that of a multipurpose domain attached to a variety of unrelated proteins, thus forming molecules with different functions (126). This pathway has allowed structurally distinct Hbs to evolve: (i) to protect against the high levels of nitrosative stress of the earth's early environment; (ii) to protect against O 2 -linked oxidation; (iii) to act as O 2 sensors that help regulate the expression of proteins during periods of hypoxia or anoxia; and (iv) to enable aerobic respiration by facilitating diffusion and/or acting as O 2 carriers (44,56,57,70,71,73,107). A common theme in the fascinating story of Hb evolution is the emergence of distinct mechanisms for controlling Hb's oxygenation and redox functions.Since increased amounts of O 2 were released in our planet's early history, O 2 toxicity brought about species extinction on a global scale. On the other hand, this ''oxygen pollution'' made possible a new biological process, that of aerobic respiration. A tremendous gain in the energy obtainable from oxidation of energy-rich metabolites was achieved when organisms evolve...

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“…However, the basic properties of cross-linked hemoglobin are closely related to the iron environment, as shown by the synthetic hemoglobin-model compound studies (Traylor and Traylor 1982;Collman et al 1975). A glutaraldehyde impact study on the heme environment would allow a better knowledge of the properties of glutaraldehyde-modified hemoglobin and its utilization as a cellular oxygen carrier.…”

Section: Introductionmentioning

confidence: 99%

Glutaraldehyde effect on hemoglobin: evidence for an ion environment modification based on electron paramagnetic resonance and Mossbauer spectroscopies

Chevalier¹,

Guillochon²,

Nedjar³

et al. 1990

Biochem. Cell Biol.

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Glutaraldehyde is a widely used reagent for hemoglobin cross-linking in blood substitutes research. However, hemoglobin polymerization by glutaraldehyde involves modifications of its functional properties, such as oxygen affinity, redox potentials, and autoxidation kinetics. The aim of this article is to investigate, by electron paramagnetic resonance and Mossbauer spectroscopies, the changes that occur in the iron environment after glutaraldehyde cross-linking. Spectrometric studies were performed with native hemoglobin and hemoglobin cross-linked as soluble and insoluble polymers. Spectrometry data comparison with glutaraldehyde-modified hemoglobin functional properties allows to interpret from a structural point of view that glutaraldehyde action occurs as a decrease of the O--N(F8His) distance, an increase of the Fe--N(F8His) bond length, and the decrease of the distal-side steric hindrance.

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Considerations for the Design of useful Synthetic Oxygen Carriers

Cited by 54 publications

References 1 publication

Acid Bohr effect of a monomeric haemoglobin from Dicrocoelium dendriticum

Acid Bohr effect of a monomeric haemoglobin from Dicrocoelium dendriticum

Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin

Glutaraldehyde effect on hemoglobin: evidence for an ion environment modification based on electron paramagnetic resonance and Mossbauer spectroscopies

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