This paper is only available as a PDF. To read, Please Download here.
Abstract
Comparisons were made of drug-induced oxidation of purified hemoglobins A, S, E, and
F. Repetitive spectral scans of reaction mixtures containing menadione showed that
Hb E was the most reactive and Hb F was the least reactive of the hemoglobins studied.
Hb E oxidation was only slightly faster than normal, but it produced much larger relative
quantities of low-spin ferric hemoglobin (hemichromes). Hb F oxidation was considerably
slower than normal but produced normal amounts of hemichromes relative to methemoglobin.
Precipitation occurred in the order E > S > A > F. The abnormally slow rate of Hb
F oxidation was even more striking when the oxidant was acetylphenylhydrazine (APH),
and the sensitivity of the reaction to catalase was severely diminished. These hemoglobins
thus exhibit entirely different reaction profiles during drug-induced oxidation. The
amino acid substitution in Hb E alters the globin tertiary structure, so that hemichromes
can more readily form, whereas the decreased susceptibility to oxidative denaturation
of Hb F appears related to the absence of a site that normally reacts with hydrogen
peroxide to increase oxidation rate. Such Hb F stability is consistent with the mild
phenotypic expression of doubly heterozygous β-thalassemia/ HPFH and Hb S/HPFH. The
role of Hb E instability in altered red cell morphology relative to the thalassemia-like
deficit of β globin mRNA has not been entirely resolved. Nevertheless, the clinical
repercussions of the abnormal properties of Hb E are mild, and they may be involved
with the prevalence of this hemoglobin in Southeast Asia as a balanced polymorphism
in which the advantage to hétérozygotes is, as yet, unclear.
Abbreviations:
(Hb E) (hemoglobin E), (Hb S) (hemoglobin S), (Hb A) (hemoglobin A), (Hb F) (hemoglobin F), (HPFH) (hereditary persistence of fetal hemoglobin), (APH) (acetylphenylhydrazine), (P50) (oxygen tension at which hemoglobin is half saturated), (mRNA) (messenger RNA), (NADH) (nicotinamide adenine dinucleotide reduced), (DEAE) (diethylaminoethyl), (EDTA) (ethylenediamine tetraacetic acid), (-SH group) (sulfhydryl group)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Translational ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Hemoglobin Hasharon (α247his(CD5)β2): a hemoglobin found in low concentration.J Clin Invest. 1969; 48: 834
- Mechanical instability of the oxy-form of sickle haemoglobin.Nature. 1973; 244: 437
- Abnormal precipitation of oxyhemoglobin S by mechanical shaking.in: ed. 2. Proc Natl Acad Sci USA. 71. 1974: 1594
- Drug-induced oxidation and precipitation of hemoglobins A, S and C.Biochim Biophys Acta. 1982; 701: 39
- Comparison of the effects of lower monohydric alcohols and inositol hexaphosphate on the oxidation of hemoglobin by menadione.Biochim Biophys Acta. 1982; 705: 48
- Conformational effects of the Hb S mutation.in: Caughey WS Biochemical and Clinical Aspects of Hemoglobin Abnormalities. Academic Press, Inc, New York1978: 299
- Conformational changes in the hemoglobin S system as seen by proton binding.J Biol Chem. 1980; 255: 8592
- Hemoglobin E, an oxidatively unstable mutation.J Lab Clin Med. 1975; 85: 531
- A simple method for the detection of unstable haemoglobins.Br J Haematol. 1972; 23: 615
- Identification of hemoglobin E by the isopropanol solubility test.Clin Biochem. 1980; 13: 146
- Molecular pathology of human haemoglobin.Nature. 1968; 219: 902
- Studies on hemoglobin E. I. The clinical, hematologic, and genetic characteristics of the hemoglobin E syndromes.J Lab Clin Med. 1956; 47: 455
- Homozygous hemoglobin E mimics β-thalassemia minor without anemia or hemolysis: hematologic, functional, and biosynthetic studies of first north American cases.Am J Hematol. 1980; 8: 109
- Defective synthesis of Hb E is due to reduced levels of βE mRNA.Nature. 1980; 288: 497
- Molecular analysis of the β-thalassemia phenotype associated with inheritance of hemoglobin E (α2β226Glu → Lys).J Clin Invest. 1981; 68: 118
- Instability of βE-messenger RNA during erythroid cell maturation in hemoglobin E homozygotes.J Clin Invest. 1982; 69: 1050
- Abnormal RNA processing due to the exon mutation of βE-globin gene.Nature. 1982; 300: 768
- Mechanism of denaturation of haemoglobin by alkali.Nature. 1974; 247: 341
- Formation of ferrihaemoglobin of isolated human haemoglobin types by nitrite.Nature. 1963; 200: 898
- Effects of hemoglobin F levels, KCN, and storage on the isopropanol precipitation test for unstable hemoglobins.Am J Clin Pathol. 1976; 66: 878
- Deficient activity of DPNH-dependent methemoglobin diaphorase in cord blood erythrocytes.Blood. 1963; 21: 51
- Vergleichende Untersuchung der Spontanoxydation des Blutfarbstoffes in Nabelschnur—und Erwachsenenerythrocyten nach Glykolysehemmung.Acta Haematol. 1956; 16: 137
- Human Hemoglobins.in: W. B. Saunders Co, Philadelphia1977: 181
- The Thalassemia Syndromes.in: ed. 2. Blackwell Scientific Publications, Oxford1972: 202
- The demonstration of ferrihemochrome intermediates in Heinz body formation following the reduction of oxyhemoglobin A by acetylphenylhydrazine.Biochim Biophys Acta. 1975; 393: 404
- Mechanism of oxyhaemoglobin breakdown on reaction with acetylphenyhydrazine.Biochem J. 1978; 173: 19
- The reaction of menadione with haemoglobin.Biochem J. 1979; 179: 665
- Equations for the spectrophotometric analysis of hemoglobin mixtures.Anal Biochem. 1973; 55: 245
- Reactions involving superoxide and normal and unstable haemoglobins.Biochem J. 1976; 155: 493
- Studies on the heterogeneity of hemoglobin. IX. The use of Tris (hydroxy-methyl) aminomethane-HCL buffers in the anion-exchange chromatography of hemoglobins.J Chromatogr. 1965; 19: 160
- The biosynthesis of human hemoglobin A1C slow glycosylation of hemoglobin in vivo.J Clin Invest. 1976; 57: 1652
- The relation between the minor components of whole normal human adult hemoglobin as isolated by chromatography and starch block electrophoresis.J Am Chem Soc. 1961; 83: 1472
- Oxygen affinity and stability of hemoglobin Dunn (α6(A4)Asp → Asn): use of isoelectric focusing in recognition of a new abnormal hemoglobin.Am J Hematol. 1980; 9: 151
- Studies on the stability of oxyhemoglobin A and its constituent chains and their derivatives.J Biol Chem. 1971; 246: 3356
- Denaturation of the normal and abnormal hemoglobin molecule.in: Semin Hematol. 11. 1974: 441
- Denatured hemoglobin in sickle erythrocytes.J Clin Invest. 1977; 59: 633
- Role of haemichromes in the formation of inclusion bodies in haemoglobin H disease.Nature. 1969; 222: 248
- Characterization of Heinz bodies in unstable haemoglobin haemolytic anaemia.Nature. 1972; 240: 150
- Studies of haemoglobin denaturation and Heinz body formation in the unstable hemoglobins.J Clin Invest. 1974; 54: 678
- Involvement of superoxide anion in the reaction of mechanism of haemoglobin oxidation by nitrite.Biochem J. 1981; 193: 169
- Involvement of peroxide and superoxide in the oxidation of hemoglobin by nitrite.Biochem Biophys Res Commun. 1982; 105: 127
- Mechanism for the autoxidation of hemoglobin by phenols, nitrite and “oxidant” drugs. Peroxide formation by one electron donation to bound dioxygen.Biochem Biophys Res Commun. 1975; 62: 561
- Oxidative hemolysis and precipitation of hemoglobin. II. Role of thiols in oxidant drug action.J Clin Invest. 1961; 40: 454
- Products of oxidation of a protein thiol group after reaction with various oxidizing agents.Arch Biochem Biophys. 1967; 122: 406
- The effect on subtilisn activity of oxidizing a methionine residue.J Biol Chem. 1969; 244: 5333
- Oxygen radicals, hydrogen peroxide, and oxygen toxicity.in: Pryor WA Free Radicals in Biology. Academic Press, Inc, New York1976: 239
- Oxidation-reduction potentials of human fetal hemoglobin and γ chains. Effects of blocking sulfhydryl groups.J Biol Chem. 1975; 250: 3929
- Hemoglobin E trait reexamined: a cause of microcytosis and erythrocytosis.Blood. 1979; 53: 109
Article info
Publication history
Accepted:
July 5,
1983
Received:
March 18,
1983
Footnotes
☆This work was supported by grant HL02799 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Identification
Copyright
© 1983 Published by Elsevier Inc.
