Carbon monoxide binding to the ferrous chains of [Mn,Fe(II)] hybrid hemoglobins: pH dependence of the chain affinity constants associated with specific hemoglobin ligation pathways.

In mixed-metal [Mn,Fe] hybrid hemoglobins (Hb), the two chains of a single type, alpha or beta, are substituted with manganese protoporphyrin IX, which does not bind CO in either the Mn(II) or Mn(III) valency states. Thus, CO binding by the two ferrous subunits of a hybrid with Mn of either valency represents a simplified two-step Hb ligation process in which ligands bind to a single-chain type. Considering the [Mn(II),Fe(II)] hybrids, which are deoxy T-state analogues, at pH 6.6 both types bind CO with low affinity (alpha-Fe, 0.38 mmHg; beta-Fe, 0.71 mmHg) and noncooperatively (Hill coefficient n = 1). At elevated pH, both exhibit an increase in affinity (Bohr effect) and strong cooperativity, with the alpha-Fe hybrid having a higher degree of cooperativity (n approximately equal to 1.6) than beta-Fe (approximately equal to 1.3) at pH 9.0. The CO association constants for the Hb ligation routes in which the first two ligands bind to the same chain type are obtained from these measurements, and their pH dependence provides estimates of the proton release at each step. Through studies of CO on- and off-rates, the [Mn(III),Fe(II)] hybrids are used to obtain the pH dependence of the association constants for binding the fourth CO to the individual Hb chains.(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  G. Weber.  Asymmetric ligand binding by haemoglobin , 1982, Nature.

[2]  B. Hoffman,et al.  Equilibrium and Kinetic CO Binding Parameters of T- and R-State Hemoglobin Chains Using Iron-Manganese Hybrids , 1982 .

[3]  G. K. Ackers,et al.  Mutual effects of protons, NaCl, and oxygen on the dimer-tetramer assembly of human hemoglobin. The dimer Bohr effect. , 1981, The Journal of biological chemistry.

[4]  A. Kajita,et al.  Changes in pKa values of individual histidine residues of human hemoglobin upon reaction with carbon monoxide. , 1980, Biochemistry.

[5]  M. Ikeda-Saito,et al.  Studies on cobalt myoglobins and hemoglobins: XI. The interaction of carbon monoxide and oxygen with α and β subunits in iron-cobalt hybrid hemoglobins☆☆☆ , 1980 .

[6]  L. Parkhurst.  Hemoglobin and Myoglobin Ligand Kinetics , 1979 .

[7]  K. Imai,et al.  Thermodynamic aspects of the co-operativity in four-step oxygenation equilibria of haemoglobin. , 1979, Journal of molecular biology.

[8]  Q. Gibson,et al.  Cooperative nitric oxide binding by manganese hemoglobin. Implications for the role of steric control in hemoglobin ligation. , 1979, The Journal of biological chemistry.

[9]  K. Nishikura.  Identification of histidine-122alpha in human haemoglobin as one of the unknown alkaline Bohr groups by hydrogen--tritium exchange. , 1978, The Biochemical journal.

[10]  J. Baldwin,et al.  Role of Bohr group salt bridges in cooperativity in hemoglobin. , 1978, Biochimica et biophysica acta.

[11]  W. Scheidt.  Trends in metalloporphyrin stereochemistry , 1977 .

[12]  A. Tan-Wilson,et al.  Kinetic studies on the binding affinity of human hemoglobin for the 4th carbon monoxide molecule, L4. , 1976, The Journal of biological chemistry.

[13]  V. Sharma,et al.  Dissociation of CO from carboxyhemoglobin. , 1976, The Journal of biological chemistry.

[14]  K. Moffat,et al.  The structure of metmanganoglobin. , 1976, Journal of molecular biology.

[15]  R G Shulman,et al.  Allosteric interpretation of haemoglobin properties , 1975, Quarterly Reviews of Biophysics.

[16]  C. Reed,et al.  Manganese(II) porphyrins. Synthesis, structures, and preference for five-coordination , 1975 .

[17]  R. Dinello,et al.  Analytical chromatography of hemins on silica gel. , 1975, Analytical biochemistry.

[18]  S. Edelstein,et al.  MANGANESE‐SUBSTITUTED HEMOGLOBIN AND MYOGLOBIN * , 1975, Annals of the New York Academy of Sciences.

[19]  T. Yonetani,et al.  PH dependence of the Adair constants of human hemoglobin. Nonuniform contribution of successive oxygen bindings to the alkaline Bohr effect. , 1975, The Journal of biological chemistry.

[20]  M. Karplus,et al.  Analysis of cooperativity in hemoglobin. Valency hybrids, oxidation, and methemoglobin replacement reactions. , 1975, Biochemistry.

[21]  S. Edelstein,et al.  Extensions of the allosteric model for hemoglobin. II. Consequences of functional nonequivalence of the alpha and beta chains. , 1974, Biochemistry.

[22]  C. Ho,et al.  Effects of ligands and organic phosphates on functional properties of human adult hemoglobin. , 1974, Biochemistry.

[23]  S. Edelstein,et al.  Manganese hemoglobin: allosteric effects in stopped flow flash photolysis and sedimentation measurements. , 1974, Biochemical and biophysical research communications.

[24]  J. J. Breen,et al.  Direct measurement of the pK values of an alkaline Bohr group in human hemoglobin. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[25]  K. Imai.  Analyses of oxygen equilibria of native and chemically modified human adult hemoglobins on the basis of Adair's stepwise oxygenation theory and the allosteric model of Monod, Wyman, and Changeux. , 1973, Biochemistry.

[26]  Q. Gibson,et al.  The kinetics of ligand binding to hemoglobin valency hybrids and the effect of anions. , 1972, The Journal of biological chemistry.

[27]  M. Waterman,et al.  Studies on modified hemoglobins. I. Properties of hybrid hemoglobins containing manganese protoporphyrin IX. , 1970, The Journal of biological chemistry.

[28]  F. Kampas,et al.  On the preparation of metalloporphyrins , 1970 .

[29]  E. Antonini,et al.  The binding of carbon monoxide by human hemoglobin. Proof of validity of the spectrophotometric method and direct determination of the equilibrium. , 1968, The Journal of biological chemistry.

[30]  J. Changeux,et al.  ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. , 1965, Journal of molecular biology.

[31]  Q. Gibson,et al.  Kinetics of carbon monoxide binding to manganese, zinc, and cobalt hybrid hemoglobins , 1980 .

[32]  T. E. Phillips,et al.  Electronic control of ferroporphyrin ligand-binding kinetics , 1980 .

[33]  B. Hoffman,et al.  Metal-substituted hemoglobin and other hemoproteins. , 1978, Methods in enzymology.

[34]  Y. Yip,et al.  Reconstitution of native human hemoglobin from separated globin chains and alloplex intermediates. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[35]  J. Baldwin.  Structure and function of haemoglobin. , 1975, Progress in biophysics and molecular biology.

[36]  S. Edelstein.  Cooperative interactions of hemoglobin. , 1975, Annual review of biochemistry.

[37]  H. Mcconnell,et al.  The binding of a spin-labeled triphosphate to hemoglobin. , 1972, Cold Spring Harbor symposia on quantitative biology.