One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) ...One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) takes care of the Hb physiologically leaked into the plasma-it binds Hb and makes it much less toxic while retaining the Hb’s high oxygen transporting capacity.We used Electron Paramagnetic Resonance(EPR) spectroscopy to show that the protein bound radical induced by H2O2 in Hb and Hp-Hb complex is formed on the same tyrosine residue(s),but,in the complex,the radical is found in a more hydrophobic environment and decays slower than in unbound Hb,thus mitigating its oxidative capacity.The data obtained in this study might set new directions in engineering blood substitutes for transfusion that would have the oxygen transporting efficiency typical of Hb,but which would be non-toxic.展开更多
基金supported by the Biomedical EPR Facility of the University of Essexgranted by the EPSRC funded UK National Service for Computational Chemistry Software(NSCCS,1996-2017)Imperial College London。
文摘One of the difficulties in creating a blood substitute on the basis of human haemoglobin(Hb) is the toxic nature of Hb when it is outside the safe environment of the red blood cells.The plasma protein haptoglobin(Hp) takes care of the Hb physiologically leaked into the plasma-it binds Hb and makes it much less toxic while retaining the Hb’s high oxygen transporting capacity.We used Electron Paramagnetic Resonance(EPR) spectroscopy to show that the protein bound radical induced by H2O2 in Hb and Hp-Hb complex is formed on the same tyrosine residue(s),but,in the complex,the radical is found in a more hydrophobic environment and decays slower than in unbound Hb,thus mitigating its oxidative capacity.The data obtained in this study might set new directions in engineering blood substitutes for transfusion that would have the oxygen transporting efficiency typical of Hb,but which would be non-toxic.
