摘要:

To date 88 abnormal hemoglobins have been described with altered oxygen affinities. Of these, 60 variants have high affinity and 28 have low affinity. Twenty-six of these abnormal hemoglobins are chemically unstable. Twenty-seven of the high affinity hemoglobins are associated with erythrocytosis. An equal number are not associated with increased red cell mass. Anemia has been reported with 13 of the low affinity variants; however, the primary cause of the anemia of many may be the concurrent chemical instability. A strong correlation can be shown for stable variants with altered oxygen affinity between the P50value of the red cell and the hemoglobin concentration of the affected individual's blood.Hemoglobin variants with altered oxygen affinity can be classified into groups depending upon the amino acid change in specific structural sites. The sites include subunit interfaces, heme contacts, central cavity, DPG binding site, C-terminus, and other external and internal residues.Functional studies of six abnormal hemoglobins, four at theβ101 residue in the central cavity near theα1β2interface, one near the DPG binding site and one at the C-terminus of theβchain, indicate that the exact explanation of the structure-function relationship in hemoglobin depends upon the specific residue that is altered and the chemical properties of the substituted group. Comparative studies of multiple variants of the same position should provide insight into the role of critical residues in the binding of oxygen by hemoglobin.

ISSN:0363-0269    

DOI:10.3109/03630268008996208

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

Oxygen binding properties of fifteen kinds of abnormal hemoglobins discovered in Japan were elucidated with the automatic oxygenation apparatus which was developed by Imai et al. This paper reviews the functional characteristics of those hemoglobins previously reported, presents functional data of some newly studied hemoglobins, and gives a discussion on structure-function relationships in those hemoglobins. This paper also describes a simple procedure for generating a predicted oxygen equilibrium curve of non-isolatable hemoglobin from equilibrium curves of normal hemolysate and hemolysate containing that hemoglobin.

ISSN:0363-0269    

DOI:10.3109/03630268008996209

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

The two-state model of Monod, Wyman and Changeux has been used extensively in analysis of the functional behavior of human hemoglobin. Within the context of this model, the cooperativity, pH dependence of oxygen binding, and anionic regulation of oxygen affinity are all considered to be due to shifts in the equilibrium between low affinity (T) conformational states and high affinity (R) confor-mational states. The heterotropic effectors, such as protons, carbon dioxide, inorganic anions, and organic polyphosphates, are considered to be principally active in causing shifts in the alloste-ric equilibrium constant L. For both simple anions, such as chloride, and strong effectors, such as inositol hexaphosphate, the allosteric equilibrium constant L increases with increasing concentrations of the effector.

ISSN:0363-0269    

DOI:10.3109/03630268008996210

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

Hemoglobin M Iwate is a mutant in which the proximal histidine residue (F8) of theαchain is replaced by tyrosine. One of consequences of this mutation is the oxidation of the iron atom of theαchain, while theβchain of the tetramer remains in the ferrous state, capable of binding oxygen. NMR experiments (1) and X ray analysis (2) have shown that the quaternary structure of this mutant hemoglobin is almost frozen in the T state, no matter whether its normalβhemes are unliganded or liganded, in solution as well as in the crystal. Baldwin has estimated the allosteric equilibrium constant for Hb M Iwate in phosphate buffer as about 105in favor of the T state (3). It was of interest, therefore, to see the effect of organic phosphate on the oxygen equilibrium function of ferrousβhemes of the mutant.

ISSN:0363-0269    

DOI:10.3109/03630268008996211

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

Hb Volga (β27 Ala→Asp) on the basis of physical tests is only a mildly unstable hemoglobin yet it is associated with a gross re-ticulocytosis. This is partly explicable by an increased oxygen affinity with a compensating erythrocytosis but there is also brisk hemolysis. It is not certain that this hemolysis is due to precipitation of the hemoglobin asin vitroinclusion body formation is not remarkable and there is no evidence of preferential proteolysis of the abnormal subunits, at least in the reticulocytes. There is increased autoxidation and it may be the consequence of this that is the prime cause of hemolysis.

ISSN:0363-0269    

DOI:10.3109/03630268008996212

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

Ten unstable hemoglobins have been identified in 14 Japanese families (Table I). Five of them which have never been found in other countries are Hb Hirosaki, Hb Iwata, Hb Tochigi, Hb Mizuho, and Hb Toyoake. Hb Köln has been found in four independent families. Eight cases (57% of the total number of families) appear to have occurred byde novomutation. We will briefly describe two new unstable hemoglobins, Hb Toyoake and Hb Iwata.

ISSN:0363-0269    

DOI:10.3109/03630268008996213

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

The differentiation, hematologic features and clinical manifestations of patients with the various sickling disorders are reviewed. The deficiencies in our current knowledge about the spectrum of the clinical course of patients with these conditions is discussed. The interaction ofαthalassemia with sickle cell anemia and its possible effect upon the severity of the disease is summarized. The apparent milder disease in certain groups of patients with sickle cell anemia in whom there is an associated elevation of hemoglobin F is contrasted with the controversy surrounding the effects of hemoglobin F levels in the patients of African origin.

ISSN:0363-0269    

DOI:10.3109/03630268008996214

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

During the last decade there have been major advances in understanding the structure of the gel of deoxyhemoglobin S and the mechanism of its formation. These advances have allowed the development of a new strategy for the inhibition of gelation, i.e., stereo-specific competitive inhibitors of the polymerization process. For this purpose we have used equilibrium solubility measurements to study the effects of amino acids and peptides on deoxyhemoglobin S solubility. We have found that aromatic amino acids and short peptides containing these amino acids significantly increase solubility; longer peptides, however, decrease solubility by an excluded-volume related effect. Recently we have used computer graphics projections of the surface of the hemoglobin molecules in the crystal form to design peptide inhibitors. In addition, we have developed 13Cnuclear magnetic resonance spectroscopic methods to quantitate the gel of deoxyhemoglobin S in hemoglobin solutions and in cells. These spectroscopic methods allow us to study the mechanism of intracellular gelation and to test the effects of inhibitors on sickle cells.

ISSN:0363-0269    

DOI:10.3109/03630268008996215

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

摘要:

During 7 years of screening for hemoglobin variants, over 75 rare variants have been characterized. Of these, 18 were described for the first time. This report presents tabulated data regarding the structural and functional defects that were observed, information on the ethnic origin, and other special properties exhibited by these variants. The strategy and procedures for characterizing these variants are also summarized.

ISSN:0363-0269    

DOI:10.3109/03630268008996216

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630268008996217

出版商:Taylor&Francis    

年代:1980

数据来源: Taylor