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myo ‐Inositol Trispyrophosphate: A Novel Allosteric Effector of Hemoglobin with High Permeation Selectivity across the Red Blood Cell Plasma Membrane
Author(s) -
Duarte Carolina D.,
Greferath Ruth,
Nicolau Claude,
Lehn JeanMarie
Publication year - 2010
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000499
Subject(s) - dids , band 3 , chemistry , allosteric regulation , red blood cell , hemoglobin , membrane , biophysics , taurine , intracellular , biochemistry , membrane protein , receptor , biology , amino acid
myo ‐Inositol trispyrophosphate (ITPP), a novel membrane‐permeant allosteric effector of hemoglobin (Hb), enhances the regulated oxygen release capacity of red blood cells, thus counteracting the effects of hypoxia in diseases such as cancer and cardiovascular ailments. ITPP‐induced shifting of the oxygen–hemoglobin equilibrium curve in red blood cells (RBCs) was inhibited by DIDS and NAP‐taurine, indicating that band 3 protein, an anion transporter mainly localized on the RBC membrane, allows ITPP entry into RBCs. The maximum intracellular concentration of ITPP, determined by ion chromatography, was 5.5×10 −3 M , whereas a drop in concentration to the limit of detection was observed in NAP‐taurine‐treated RBCs. The dissociation constant of ITPP binding to RBC ghosts was found to be 1.72×10 −5 M . All data obtained indicate that ITPP uptake is mediated by band 3 protein and is thus highly tissue‐selective towards RBCs, a feature of major importance for its potential therapeutic use.