[Erythrocytosis due to a high-affinity hemoglobulin: mutant hemoglobin Saint-Jacques beta 140 (H18) Ala----Thr with a change in the 2,3-diphosphoglycerate binding site].
All the high oxygen affinity variants have substitutions in regions that are crucial to hemoglobin function: mainly the alpha 1 beta 2 interface, the C-terminal end of the beta chain and the aminoacid residues involved in the 2,3 disphophoglycerate (2,3 DPG) binding site. In this report we describe a new variant with familial erythrocytosis: hemoglobin Saint-Jacques beta 140 (H18) Ala----Thr, whose main abnormality is a defect in organic phosphate binding in the central cavity between to two beta chains. This variant could not be separated from hemoglobin A by standard electrophoretic methods or by isoelectric focusing. The abnormal peptide was isolated by reverse-phase high performance liquid chromatography and the structural modification determined by manual sequencing micro-method. Functional studies on red blood cells as well as on stripped lysate showed increased oxygen affinity, normal Bohr effect, decreased heme-heme interaction and loss of the 2,3 DPG regulatory effect.
D019794:2,3-Diphosphoglycerate; D000328:Adult; D001665:Binding Sites; D004163:Diphosphoglyceric Acids / Q000097:blood*; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D009154:Mutation; D010100:Oxygen / Q000097:blood*; D011086:Polycythemia / Q000097:blood* / Q000235:genetics
D004163:Diphosphoglyceric Acids; D006455:Hemoglobins, Abnormal; D019794:2,3-Diphosphoglycerate; C040760:hemoglobin Saint Jacques; D010100:Oxygen
Polyglobulie par hémoglobine à affinité augmentée: hémoglobine Saint-Jacques beta 140 (H18) Ala----Thr, mutant présentant une altération du site de fixation du 2,3-diphosphoglycérate.