Role of Haemichromes in the Formation of Inclusion Bodies in Haemoglobin H Disease

Ea, Rachmilewitz; Peisach, Jack; Bradley, Thomas B.; Blumberg, W. E.

doi:10.1038/222248a0

Cited by 114 publications

(71 citation statements)

References 17 publications

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“…The normal heme environment in hemoproteins may therefore exist in dynamic equilibrium between these two crevice structures, and there are various experimental situations in which one or the other of the two structures may be stabilized (11,18,20,21). Our results show that pressure is one of the experimental conditions that affects the position of this equilibrium.…”

Section: Resultsmentioning

confidence: 99%

“…Pressure and heme crevice equilibria Evidence from spectroscopic (13,15), magnetic (16), and reactivity studies (17)(18)(19) suggests that methemoglobin and metmyoglobin may be an equilibrium mixture of two forms. Electron paramagnetic resonance studies at low temperature have shown that there may be a form of methemoglobin that is stabilized in frozen solutions having a characteristic spectrum of a hemichromogen (20,21). Such a structure may arise if the heme-linked ligand at the sixth coordination position is replaced by the distal histidine.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase.

Ogunmola¹,

Zipp²,

Chen³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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The spectra of the ferric form of most heme proteins [metmyoglobin, methemoglobin, horse radish peroxidase (EC 1.11.1.7), and ferricytochrome c at pH 1.5J are converted from high-spin (open crevice) structure to low-spin (closed crevice) form under pressure. Pressures up to 8000 kg/cm2 (780 MPa) have no effect on the spectra of high-spin ferro-and ferricytochrome c, which have a closed crevice structure at pH 7.0. Spectra of deoxy-ferromyoglobin and deoxy-ferrohemoglobin are reduced in intensity, but pressure does not change the positions of the absorption maxima. Cyanide ion prevents pressure-induced spectral changes in metmyoglobin and methemoglobin up to 8000 kg/cm2. Carbon monoxide (with a high affinity for the ferro heme iron) has a similar effect on ferromyoglobin and ferrohemoglobin. The pressure required to cause spectral changes in the heme proteins falls in the order, cytochrome c (pH 7.0) > horse radish peroxidase > myoglobin > hemoglobin. We have calculated a volume change of -50 cm:3/mol associated with the configurational change accompanying the reformation of the iron-methionine bond in cytochrome c at low pH.The effect of pressure on the complexes of hemoglobin (1-4) and myoglobin (5-7) have been the subject of considerable investigation over the last few years. These investigations have, however, been largely concerned with changes in the functional properties (1, 2), the thermodynamic properties accompanying the binding of ligands (6), and the denaturation of the protein (5). However, the Soret and visible spectra of hemoglobin and hemoglobin complexes (3, 4) and the visible spectra of metmyoglobin fluoride (7) show interesting changes when these molecules are subjected to hydrostatic pressure. We have extended these high pressure studies on metmyoglobin and methemoglobin and have investigated, in addition, the spectral changes in the visible region accompanying the pressurization of two other hemoproteins, cytochrome c and horse radish peroxidase (donor:hydrogen-peroxide oxidoreductase; EC 1.11.1.7). MATERIALS AND METHODSHuman hemoglobin was prepared by the usual method (8) and oxidized to methemoglobin with 2-fold excess of potassium ferricyanide. Ferrocyanide and excess ferricyanide were removed by dialysis against 0.05 M sodium chloride at pH 6.0. Sperm whale metmyoglobin and horse heart (type III) cytochrome c were obtained from Sigma Chemical Co. and were used without further purification. Buffers used were cacodylate and Tris. Tris buffer was prepared from Trizma base (Sigma) and Trizma-HCI (Sigma) that had been dried under reduced pressure before use. All methemoglobin and metmyoglobin solutions were 0.05 M in buffer ions. Hemoglobin and myoglobin were deoxygenated by addition of sodium dithionite in a glove box previously filled with dry nitrogen.High Pressure Studies. The high pressure optical bomb used was designed by Dr. W. B. Daniels and has been described elsewhere (9).At each increment of pressure, the system was allowed 5 min to attain temperature re-equilibration. Me...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase.

Ogunmola¹,

Zipp²,

Chen³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…5A, trace 2). These spectroscopic profiles are characteristic of hemichromes (41)(42)(43) and suggest that the major part of the protein, probably obtained in the form of high spin met form, has been converted to low spin hemichromes. This hypothesis is confirmed by the CO difference spectrum (Fig.…”

Section: Biochemical Characterization Of the Ynl234wp Recombinant Promentioning

confidence: 95%

Characterization of a New Hemoprotein in the YeastSaccharomyces cerevisiae

Sartori¹,

Aldegheri²,

Mazzotta³

et al. 1999

Journal of Biological Chemistry

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The Saccharomyces cerevisiae gene YNL234w encodes a 426-amino acid-long protein that shares significant similarities with the globin family. Compared with known globins from unicellular organisms, the Ynl234wp polypeptide is characterized by an unusual structure. In this protein, a central putative heme-binding domain of about 140 amino acids is flanked by two sequences of about 160 and 120 amino acids, respectively, which share no similarity with known polypeptides. Northern analysis indicates that YNL234w transcription is very low in cells grown under normal aerobic conditions but is induced by oxygen-limited growth conditions and by other stress conditions such as glucose repression, heat shock, osmotic stress, and nitrogen starvation. However, the deletion of the gene had no detectable effect on yeast growth. The Ynl234wp polypeptide has been expressed in Escherichia coli, and the hemoprotein nature of the recombinant protein was demonstrated by heme staining after SDS/polyacrylamide gel electrophoresis and spectroscopic analysis. Our data indicate that purified recombinant Ynl234wp possesses a noncovalently bound heme molecule that is predominantly found in a low spin form.

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“…The correlations between the occurrence of hemichromes and the formation of channels of access to the solvent in vertebrate hemoglobins are well established (Robinson et al, 2003;Pesce et al, 2004). Furthermore, this mechanism has been associated to higher processes of denaturation and hemolytic anemia, which is characterized by the hemoglobin precipitation in the hemichrome form that constitutes the so called "Heinz Bodies" (Rachmilewitz et al, 1969;Robinson et al, 2003;Pesce et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Actually, an analysis based on Walker's Classification (Walker, 1999;Walker 2004) could furnish more detailed information regarding the occurrence of hemichromes in human hemoglobins, which are associated to the appearance of "Heinz Bodies" and hematological diseases (Rachmilewitz et al, 1969). In fact, few data are found in the literature with respect to the different species of hemichrome in human hemoglobins, which could improve the understanding of several relevant pathological processes of the vertebrates.…”

Section: Discussionmentioning

confidence: 99%

Ferric species of the giant extracellular hemoglobin of Glossoscolex paulistus as function of pH: An EPR study on the irreversibility of the heme transitions

Moreira¹,

Poli²,

Lyon³

et al. 2008

Comparative Biochemistry and Physiology Part B: Biochemistry an

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Role of Haemichromes in the Formation of Inclusion Bodies in Haemoglobin H Disease

Cited by 114 publications

References 17 publications

Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase.

Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase.

Characterization of a New Hemoprotein in the YeastSaccharomyces cerevisiae

Ferric species of the giant extracellular hemoglobin of Glossoscolex paulistus as function of pH: An EPR study on the irreversibility of the heme transitions

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