Modification of human haemoglobin with glucose 6-phosphate enhances tetramer-dimer subunit dissociation.
Studies using equilibrium gel-permeation chromatography demonstrate that formation of the covalent adduct of D-glucose 6-phosphate (G6P) with human haemoglobin promotes dissociation of the haemoglobin tetramer into its component alpha beta dimer pairs [Kdoxy = 2.57 X 10(-6) versus Kdoxy (G6P) = 11.22 X 10(-6) M-haem]. On the other hand, Kd for glucosylated haemoglobin is identical with those of the O2- and CO-liganded forms of intact haemoglobin A0. These data are consistent with the phosphate moiety alone being responsible for a 4.5-fold increase in the tetramer-to-dimer apparent Kd. This suggests the glucose 6-phosphate moiety does not bind to the same sites on haemoglobin as do the free organic phosphates, as suggested by ligand-binding kinetics data or structural analysis. My study presents a working model for studying changes in protein subunit assembly as altered by protein phosphorylations.
D001665:Binding Sites; D002263:Carboxyhemoglobin / Q000378:metabolism; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D010108:Oxyhemoglobins / Q000378:metabolism; D010766:Phosphorylation
D005958:Glucosephosphates; D006454:Hemoglobins; D046911:Macromolecular Substances; D010108:Oxyhemoglobins; D019298:Glucose-6-Phosphate; D002263:Carboxyhemoglobin