Jun Sugihara

Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.

We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere apparently shifts the allosteric equilibrium toward the low affinity state, it greatly diminishes the cofactor effects by anions. The oxygen affinity of the patients erythrocytes is substantially lowered by the presence of bezafibrate, which combines with sites different from those of 2,3-diphosphoglycerate in either hemoglobin Rahere or hemoglobin A.

Identification of an abnormal hemoglobin with reduced oxygen affinity by high-performance liquid chromatography

Abstract High-performance liquid chromatography on a reversed-phase column was applied to the structural study of the rare hemoglobin variant found in a Japanese family, which was then identified as Hb New York [113(G15) β valine → glutamic acid]. A reduced oxygen affinity is associated with this amino acid substitution, the difference in log P 50 being 0.1 at pH 7.46. The substitution of a glutamyl residue for valine may destabilize the α 1 β 1 contacts in the oxyhemoglobin structure, shifting the allosteric equilibrium towards the T form.

Hemoglobin G Waimanalo: α64 (E13) Aspartic Acid + Asparagine Observed in a Japanese Family

Hemoglobin G Waimanalo, in which an asparagine residue is substituted for an aspartic acid at position 64 (E13) of the a-chains, was found in a Japanese family. The propositus was a 40-year-old man with normal hematological parameters. Electro-phoresis of the hemolysates on a cellulose acetate sheet detected a hemoglobin variant that migrated slower than Hb A. The relative mobility was -4.88 at pH 8.6 (1). The variant, Hb A2, and Hb F comprised 24.1%, 2.0%, and 1% of the total hemoglobins, respectively (2).

A new electrophoretic variant of hemoglobin (Ogi) in which a leucine residue is replaced by an arginine residue at position 34 of the α-chain

Hemoglobin Ogi, in which an arginine is substituted for a leucine residue at position 34 of the alpha-chain, was detected in a Japanese family. Although slightly increased oxygen affinity is associated with this amino acid substitution in the alpha 1 beta 1 contact, it is without obvious deleterious effect on the hematological parameters of the individuals heterozygous for this variant.

A new electrophoretic variant of Hemoglobin (Munakata) in which a lysine residue is replaced by a methionine residue at position 90 of the α-chain

Abstract Hemoglobin Munakata, in which a methionine residue is substituted for a lysine residue at position FG2(90) of the α-chain, was detected in a Japanese family. Slightly increased oxygen affinity is associated with this amino acid substitution at the α 1 β 2 contact site in the FG nonhelical segment of the α-chain.