Hemoglobin variants and activity of the (K+Cl-) cotransport system in human erythrocytes.
To determine if the activation of the (K+Cl-) cotransport system observed in hemoglobin (Hb) S- or C-containing erythrocytes is related either to a global change of isoelectric point of the Hb molecule or to the specific location of these mutations on the position 6 of the beta chain of Hb, we studied the (K+Cl-) cotransport system in erythrocytes containing beta chain variants exhibiting either the Glu----Lys substitution observed in position beta 6 in Hb C (Hb E: beta 26 Glu----Lys; Hb O-Arab: beta 121 Glu----Lys; Hb Siriraj:beta 7 Glu----Lys) or the Glu----neutral residue substitution observed in position beta 6 in Hb S (Hb G-San Jose: beta 7 Glu----Gly; Hb D Punjab or D-Los Angeles: beta 121 Glu----Gln). The K transport mediated by the (K+Cl-) cotransport was increased in AC, AS and A-Siriraj and A-San Jose red blood cells and was similar to AA control in the other variants. These results indicate that an enhanced (K+Cl-) cotransport is not a property of all positively charged Hb variants, but it is mainly associated with mutations occurring at the beta 6 or beta 7 residues. An interaction of Hb with the cell membrane mediated by the disappearance of one of the negative charged residues (Glu) at this site of the A helix of the beta chain is the most likely candidate for the persistent activation of the (K+Cl-) cotransport system in these Hb variants.
Olivieri
O
O
INSERM U91, Hopital Henri Mondor, Creteil, France.
Vitoux
D
D
Galacteros
F
F
Bachir
D
D
Blouquit
Y
Y
Beuzard
Y
Y
Brugnara
C
C
D001692:Biological Transport; D002712:Chlorides / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D005914:Globins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007526:Isoelectric Point; D009154:Mutation; D011188:Potassium / Q000097:blood*; D013329:Structure-Activity Relationship
D002712:Chlorides; D005914:Globins; D011188:Potassium