新しい異常ヘモグロビンHemoglobin Sendagi(β42 Phe→Val)の同定とその機能特性

抄録

A new unstable hemoglobin variant, Hb Sendagi (β42Phe→Val), was found in a Japanese male and his daughter both suffering from moderate hemolytic anemia. The structure of the variant was determined and the functional properties were studied. The results obtained are as follows.
1) The variant was electrophoretically silent, but the abnormal β-chain was found to emerge ahead of the normal, 6-chain when the hemolysates from the patients were applied to a reverse-phase HPLC.
2) The tryptic peptides were prepared with the variant β-chain enriched by isopropanol precipitation and column chromatography on CM-cellulose. The abnormal peptide, βT^x-5, was separated by fingerprint mapping or by reverse-phase HPLC of the tryptic peptides.
3) Sequence analyses of the abnormal peptide revealed that the phenylalanine in position 42 (CD1) of the β-chain was replaced by valine. The variant was named as Hb Sendagi according to the place where it was discovered.
4) Hb Sendagi showed a decreased stability upon heat denaturation and isopropanol precipitation tests, and was oxidized faster than Hb A by atmospheric oxygen in the presence and absence of sodium benzoate.
5) The oxygen equilibrium curves of the hemolysates from the propositus also indicated that Hb Sendagi had a lowered oxygen affinity and a normal response to 2, 3-diphosphoglycerate.