Familial secondary erythrocytosis due to increased oxygen affinity is caused by destabilization of the T state of hemoglobin Brigham (α₂β₂(Pro100Leu)).

ABSTRACT: Hemoglobin Brigham (β Pro100 to Leu) was first reported in a patient with familial erythrocytosis. Erythrocytes of an affected individual from the same family contain both HbA and Hb Brigham and exhibit elevated O₂ affinity compared with normal cells (P₅₀ = 23 mm Hg vs. 31 mmHg at pH 7.4 at 37°C). O₂ affinities measured for hemolysates were sensitive to changes in pH or chloride concentrations, indicating little change in the Bohr and Chloride effects. Hb Brigham was separated from normal HbA by nondenaturing cation exchange liquid chromatography, and the amino acid substitution was verified by mass spectrometry. The properties of Hb Brigham isolated from the patient's blood were then compared with those of recombinant Hb Brigham expressed in Escherichia coli. Kinetic experiments suggest t

SUBMITTER: Mollan TL 

PROVIDER: S-EPMC3526987 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature