New alpha 2 globin chain variant with low oxygen affinity affecting the N-terminal residue and leading to N-acetylation [Hb Lyon-Bron alpha 1(NA1)Val --> Ac-Ala].
Hemoglobin Lyon-Bron was found in two members of a family of German ascent presenting with a moderate normocytic anemia. In this alpha 2 globin variant, the N-terminal valine of the chain was replaced by an alanine. Electrospray mass spectrometry of the alpha chain showed that, as normally, the initiator methionine was cleaved during globin processing but that the N alpha-terminal group was totally acetylated. This resulted in structural modifications of a region crucial for oxygen binding. As a consequence, hemoglobin Lyon-Bron displayed both a reduced chloride effect and a decreased oxygen affinity, this last point explaining the apparent anemia.
Lacan
P
P
Unité de Pathologie Moléculaire, Département de Biochimie, Hôpital Edouard Herriot, Lyon, France.
Souillet
G
G
Aubry
M
M
Promé
D
D
Richelme-David
S
S
Kister
J
J
Wajcman
H
H
Francina
A
A
D000107:Acetylation; D000293:Adolescent; D019943:Amino Acid Substitution; D001665:Binding Sites / Q000235:genetics; D002713:Chlorine / Q000378:metabolism; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D005914:Globins / Q000737:chemistry / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D010108:Oxyhemoglobins; D021241:Spectrometry, Mass, Electrospray Ionization; D017186:Titrimetry
D006455:Hemoglobins, Abnormal; D008024:Ligands; D010108:Oxyhemoglobins; C451961:hemoglobin Lyon-Bron; D002713:Chlorine; D005914:Globins; D010100:Oxygen