title: Hemoglobin Redondo [beta 92(F8) His----Asn]: an unstable hemoglobin variant associated with heme loss which occurs in two forms.
abstract: 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.
authors.affiliation: INSERM U299, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
authors.forename: H
authors.initials: H
authors.lastname: Wajcman
authors.forename: C
authors.initials: C
authors.lastname: Vasseur
authors.forename: Y
authors.initials: Y
authors.lastname: Blouquit
authors.forename: D E
authors.initials: DE
authors.lastname: Santo
authors.forename: M J
authors.initials: MJ
authors.lastname: Peres
authors.forename: M C
authors.initials: MC
authors.lastname: Martins
authors.forename: C
authors.initials: C
authors.lastname: Poyart
authors.forename: F
authors.initials: F
authors.lastname: Galacteros
mesh_terms: 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
chemical_list: D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; C071419:hemoglobin Redondo