Hemoglobin Redondo [beta 92(F8) His----Asn]: an unstable hemoglobin variant associated with heme loss which occurs in two forms.
Hb Redondo [beta 92(F8) His----Asn] illustrates how post-translational structural modifications may modify the phenotypic expression of an unstable hemoglobin. This variant was found in a Portuguese patient suffering from a chronic hemolytic anemia. The electrophoretic pattern demonstrated that it occurred in two forms, both being semi-hemoglobins: the fastest one migrating like HbS and the other like HbA2; after a few days of storage at 4 degrees C the intensity of the slowest Hb fraction decreased while that of the other increased proportionally. In both cases, the RP-HPLC analysis of the tryptic digest of the aminoethylated beta chains demonstrated the presence of an abnormal beta T10 peptide carrying a His----Asx substitution. Microsequence study of these two peptides demonstrated that the slowest abnormal Hb fraction had a beta 92 His----Asn substitution and the fastest a His----Asp at the same site. All these results suggest that the beta 92 His----Asn variant loses readily its heme group and that a deamidation occurs rapidly in vitro, yielding a beta 92 Asp semi-hemoglobin. The oxygen affinity of the patient's red blood cells was increased, leading to a stimulation of erythropoiesis and to a macrocytic hemolytic disease.
Wajcman
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INSERM U299, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
Vasseur
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C
Blouquit
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Y
Santo
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DE
Peres
M J
MJ
Martins
M C
MC
Poyart
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C
Galacteros
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F
D000595:Amino Acid Sequence; D000743:Anemia, Hemolytic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002908:Chronic Disease; D004355:Drug Stability; D004587:Electrophoresis, Agar Gel; D006454:Hemoglobins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry*; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D013053:Spectrophotometry
D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; C071419:hemoglobin Redondo