Lecture 6 Hemoglobin-1 class

The bohr effect co 2 66 77 88 co 2 release and

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The Bohr Effect: CO 2 66% 77% 88%
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CO 2 release and carbamate formation N-terminal amino groups react with CO 2 to form carbamic acid which dissociates into a carbamate ion and H + . The carbamate is negatively charged and forms salt bridges that stabilize the T state which is not possible when the amino termini are not modified. the formation of a carbamate yields a proton which can also contribute to the Bohr effect The stabilization of the T state of Hb through salt bridge formations leads to subsequent release of O 2 14% of CO 2 is transported from tissues to lungs in this manner. Carbamate H + Carbamic acid
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a R141 a Arg141 a Lys139 a Val1 Similar interactions to above C a N a C a N a Formation of a carbamate gives the N-terminus a negative charge instead of the usual positive charge. Salt bridge interactions occur between the negative N-terminus of one a -subunit (Val 1) and the C-terminus side chain residues of the opposite a -subunit (Lys139 or Arg141) Position of carbamate salt bridges Image accessed on May 22, 2014
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An allosteric regulator determines the Oxygen affinity of Hemoglobin T state is unstable Equilibrium lies towards R state Thus, for sufficient O 2 to be released, something must stabilize the T state 2,3-bisphosphoglycerate or (2,3-BPG) 2,3-BPG is a negatively charged molecule with the same [molar] as Hb that binds to the positively charged central cavity/pocket in the hemoglobin tetramer. This cavity exists only when hemoglobin is in the T state. 2,3-BPG
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2,3-BPG binds to the central cavity of Hb Deoxy Hb Oxy Hb Surface Contour Image: The negative charges of BPG interact with several positively charged groups (shown in blue) that surround the pocket between the β subunits on the surface of deoxyHb (T state). The binding pocket for BPG disappears on oxygenation, following transition to the R state. Thus, when the partial pressure of O 2 is high enough, the conformational change reduces the size of the cavity and 2,3-BPG no longer fits and is expelled.
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An allosteric regulator determines the Oxygen affinity of Hemoglobin 2,3-Bisphosphoglycerate binds to the central cavity of deoxyhemoglobin. It electrostatically interacts with three positively charged groups on each β chain
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O 2 binds more tightly to pure isolated Hb than to Hb in the presence of red blood cells (RBC) A higher partial pressure of O 2 is required to saturate Hb in the presence of 2,3-BPG Hb remains in the lower- affinity T state until higher [O 2 ] are reached. RBC contain 2,3-BPG which allosterically regulates the protein Without 2,3-BPG, Hb would only be able to release 8% of the O 2 instead of 66%. An allosteric regulator determines the Oxygen affinity of Hemoglobin
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Summary of 2,3-BPG allosteric regulation of Hb 2,3-BPG binds at a site other than the binding site of O 2 an allosteric effector. An allosteric effector regulates the protein by inducing a conformational change 2,3-BPG binds only to deoxyhemoglobin or T state since the allosteric binding site (in the centre of the tetramer) is absent in the R state Upon transition from T to R state, the pocket collapses (interactions are broken) and 2,3 BPG is released.
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