Studies on the Relations between Molecular and Functional Properties of Hemoglobin

Antonini, Eraldo; Wyman, Jeffries; Brunori, Maurizio; Fronticelli, Clara; Bucci, Enrico; Rossi‐Fanelli, A.

doi:10.1016/s0021-9258(18)97543-5

Cited by 143 publications

(49 citation statements)

References 11 publications

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“…It is usually assumed that although the isoelectric point is highly temperature dependent (Reeves, 1976), the overall shape of the hemoglobin titration curve is unaffected by temperature (Dalmark, 1975;Rodeau and Malan, 1979;Wolf, 1982). However, titration data for purified oxyhemoglobin obtained by Antonini et al (1965) clearly indicate an increase in the absolute value of -dz m/dpH with temperature (for pH values <7.2) that is not fully accounted for by transposition of the titration curve on the pH scale with temperature correction for the isoelectric point.…”

Section: Discussionmentioning

confidence: 96%

“…37) allows evaluation of the buffering capacity of hemoglobin as a function of pH, and at pH 7.2 -dz Hb/dpH was calculated as 10.8 proton charges/pH unit per tetramer. Available estimates of the buffering capacity of purified carboxyhemoglobin at this pH are 9.8 at 25~ (Rollema et al, 1975), 10 at 0~ (Gary-Bobo and Solomon, 1968), and 12.7 at 40~ (Antonini et al, 1965). By estimating hemoglobin buffering in a hemolysate at 37~ we have more closely approximated the physiological situation than titration experiments using highly diluted (0.15 mM) hemoglobin in NaCI or KC1 solutions.…”

Section: Discussionmentioning

confidence: 99%

“…As hemoglobin is the dominant noncarbonate buffering species in the blood, any mathematical description of the pH buffering function of the erythrocyte requires an accurate titration curve for this protein. Although the buffering characteristics of hemoglobin have been studied extensively, both theoretically (Mathew et al, 1979) and by titration of purified hemoglobin (Antonini et al, 1965;Rollema et al, 1975), few data obtained at 37"C are available. Due to extensive variation in the molecular environment of the titrating histidine residues (Mathew et al, 1979), the effect of temperature on their apparent dissociation constants, and so on the hemoglobin titration curve, is diffficult to predict.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of an electrochemical model of erythrocyte pH buffering using 31P nuclear magnetic resonance data.

Raftos

Bulliman

Kuchel

1990

The Journal of General Physiology

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When erythrocytes are suspended in a solution of known composition the resultant values of such basic cell parameters as volume and pH are difficult to predict. To facilitate such predictions, we developed a mathematical model describing the passive transmembrane distribution of permeant species; three simultaneous equations were produced. Certain essential data required for the model were determined experimentally; these included the pH dependence of the charge on the hemoglobin molecule and the variation of the osmotic coefficient of hemoglobin with cell volume. Finally, cells were added to various solutions, and then titrated to produce a wide pH range (pH 6-8). We measured the resultant cell volume, cellular and extracellular pH using both conventional and Sip NMR methods. The expected equilibrium values of these electrochemical parameters were also calculated by solving (numerically) the three model equations. The accuracy of the model simulations was evaluated by direct comparison of calculated and experimentally determined values.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of an electrochemical model of erythrocyte pH buffering using 31P nuclear magnetic resonance data.

Raftos

Bulliman

Kuchel

1990

The Journal of General Physiology

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“…Previous experimental work on thermodynamics of the oxygen-linked Bohr effect has revealed two notable features: (a) The apparent heat of Bohr proton release was unexpectedly large, i.e. 11 -15 kcal/mol of H+ at pH 7.4 (Antonini et al, 1965;Chipperfield et al, 1967;Rollema et al, 1975;Chu et al, 1984). This magnitude exceeds the standard ionization heats for amino acid side chains that are expected to contribute (i.e., with pATa values in the range 6.5-8, such as histidines or N-terminal amino groups).…”

Section: Correlation Of Cooperative Enthalpies With Bohr Protonmentioning

confidence: 99%

Enthalpic and Entropic Components of Cooperativity for the Partially Ligated Intermediates of Hemoglobin Support a "Symmetry Rule" Mechanism

Huang¹,

Ackers²

1995

Biochemistry

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Subunit assembly reactions of hemoglobin's 10 ligation microstates have been studied as a function of temperature to evaluate the enthalpic and entropic components of cooperativity. It is found that the cooperative enthalpies and cooperative entropies distribute in close agreement with predictions of the symmetry rule mechanism (Ackers et al., 1992) previously deduced from the free energy distribution, in combination with structure-sensitive probes (Doyle & Ackers, 1992; LiCata et al., 1993; Daugherty et al., 1994). Principal findings of the present study are as follows: (1) In unligated hemoglobin (quaternary T), dimer-tetramer assembly is driven by a large negative enthalpy, whereas in the fully ligated (quaternary R) species, the driving force for quaternary assembly is entropic. For the eight intermediate ligation species, the switchover from enthalpic to entropic control follows precisely the symmetry rule predictions; i.e., switching from enthalpic to entropic control occurs at each of the six steps that create ligated heme sites on both sides of the dimer-dimer interface. The combinatorial distribution found previously with free energies does not therefore arise from coincidental enthalpy-entropy compensation that masks a more fundamental distribution. (2) The free energy of tertiary constraint delta Gtc, which pays for intradimer cooperativity prior to quaternary switching, contains large enthalpic and entropic components delta Htc and delta Stc. Like delta Gtc, these terms vanish at the second binding step within the T tetramer. It is found that delta Gtc arises from a net enthalpic dominance over an almost equally large T delta Stc. (3) The stepwise enthalpies correlate with stepwise values of Bohr protons and Bohr free energies (Daugherty et al., 1994) throughout the cascade of 16 stepwise reactions; the correlated clusters of these values follow predictions of the symmetry rule mechanism. (4) These results obtained with cyanomethemoglobin are consistent with the corresponding data on oxygenated hemoglobin which has been resolved at each stage of oxygenation.

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“…It is not clear at this time whether this effect is actually a contributor to the observed Bohr effect. The large heat of ionization of the amino group, 11-14 kcal/mole (Tanford, 1962), may or may not be compatible with the observed 7-9 kcal for the alkaline Bohr effect and approximately 0 kcal for the acid Bohr effect (Antonini et al, 1965).…”

Section: Calculationsmentioning

confidence: 99%

Proton binding and dipole moment of hemoglobin. Refined calculations

Orttung¹

1970

Biochemistry

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Studies on the Relations between Molecular and Functional Properties of Hemoglobin

Cited by 143 publications

References 11 publications

Evaluation of an electrochemical model of erythrocyte pH buffering using 31P nuclear magnetic resonance data.

Evaluation of an electrochemical model of erythrocyte pH buffering using 31P nuclear magnetic resonance data.

Enthalpic and Entropic Components of Cooperativity for the Partially Ligated Intermediates of Hemoglobin Support a "Symmetry Rule" Mechanism

Proton binding and dipole moment of hemoglobin. Refined calculations

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