Hb-Alberta or α₂β₂(101(G3) GLU→GLY), a New High-Oxygen-Affinity Hemoglobin Variant Causing Erythrocytosis

Abstract

Hb-Alberta has been found in a 51 year old Caucasian male with erythrocytosis. The substitution in this variant involves the glutamyl residue in position 101(G3) of the beta chain which is replaced by a glycyl residue. Hb-Alberta accounts for about 45% in the heterozygote, and readily forms hybrid tetramers with other hemoglobins. The oxygen affinity of Hb-Alberta is greatly increased, its Bohr effect reduced, and its subunit interaction greatly diminished.

Unstable hemoglobin Rush [beta 101(G3) Glu>Gln, HBB:c.304G>C] in a Brazilian family with moderate hemolytic anemia

“…The affinity of hemoglobin Rush is similar to that of hemoglobin A, which was also reported in the original report [2]. The other three variants have increased affinity for oxygen, reflected in erythrocytosis present in carriers of these variants [15][16][17]. The size of the amino acid residue at position 101 and its electrical charge are responsible for the oxygen affinity and the allosteric properties, respectively [4].…”

Some Rare Hemoglobin Variants with Altered Oxygen Affinities; Hb Linkoping [β36(C2)Pro→Thr], Hb Caribbean [β91(F7)Leu→Ar6], and Hb Sunnybrook [β 36(C2)Pro→Arg]

“…Hematological data were obtained with automated cell counters. Red cell lysates were analyzed by starch gel and cellulose acetate electrophoresis at alkaline pH and by citrate agar electrophoresis (5). The chromatographic properties of the variants were evaluated by cation exchange high performance 1 iquid chromatography (HPLC) (6) and by DEAE-cellulose chromatography (7).…”

Role of β/δ101Gln in Regulating the Effect of Temperature and Allosteric Effectors on Oxygen Affinity in Woolly Mammoth Hemoglobin

“…The overall quaternary structure of rHb WM is quite similar to that of Hb A . Hence, the replacement of β/δ101Gln in rHb WM would be expected to significantly alter the functional properties of this protein, as has been observed with the human mutants. − In our present study, the rHb WM mutants with β/δ101 substitutions (β/δ101Gln→Glu, Lys, or Asp) have been expressed and the effect of temperature on the O 2 affinity of these mutants has been determined. Our results demonstrate clearly that the β/δ101Gln of rHb WM participates in regulating the effect of temperature on the O 2 binding.…”

“…The primary amino acid sequence of woolly mammoth Hb differs from that of Asian elephant Hb at only one position in the α-globin chain (K5N) and three positions in the β/δ-globin chain (T12A, A86S, and E101Q), [(Table ), ]. Several human Hb mutants with replacements at the β101 position (β101Glu→Gly, Lys, Gln, Asp, or Ala) have been identified. − The oxygen binding and cooperativity properties of these mutants have demonstrated clearly the importance of this residue in regulating hemoglobin function . The β101 residue is located between the critical β99Asp and β102Asn, which form intersubunit H-bonds in the α 1 β 2 interface of Hb A .…”