Hb Arta [beta 45 (CD4) Phe-->Cys]: a new unstable haemoglobin with reduced oxygen affinity in trans with beta-thalassaemia.
The interaction of rare Hb variants with beta(0)-thalassaemia results in a quasihomozygous state where the erythrocytes contain the variant as the only major adult Hb component. Such a situation is a unique model that enables functional studies even in the case of a neutral variant that could not be isolated from Hb A. We report here an unusual patient carrying Hb Arta, a novel Hb variant [beta 45 (CD4) Phe-->Cys], in trans with beta(0)-thalassaemia gene (beta(0) 39). The aminoacid substitution at the critical CD corner of this Hb molecular renders the molecule unstable. In addition, haem is displaced in a position that favours the deoxy (T) conformation of the variant, but less than in Hb Cheverly [beta 45 (CD4) Phe-->Ser], and results in a p50 of 43 mmHg (pH 7.4, 37 degrees C) in the red cells with preservation of cooperativity. Solution studies of the almost pure Hb Arta show a 50% decrease in oxygen affinity and normal cooperativity; the Bohr effect and the interaction with organic phosphates are similar to those of Hb A. Hb Arta retains both normal homo- and heterotropic effects allowing a well-preserved oxygen transport in vivo despite a mild anaemia.
Vassilopoulos
G
G
First Department of Medicine, Laikon Hospital, Athens, Greece.
Papassotiriou
I
I
Voskaridou
E
E
Stamoulakatou
A
A
Premetis
E
E
Kister
J
J
Marden
M
M
Griffon
N
N
Poyart
C
C
Wajcman
H
H
D000328:Adult; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D004588:Electrophoresis, Cellulose Acetate; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism*; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D004247:DNA; D010100:Oxygen