5f. As stated in the article, histidine residues are important mediators of the

Question

5f. As stated in the article, histidine residues are important mediators of the Bohr effect. "In 0.1 M HEPES buffer with 0.1 M chloride, B146His contributes the most to the alkaline Bohr effect (63% at pH 7.4) among those surface histidyl residues, while 143 His contributes the most to the acid Bohr effect (71% at pH 5.1)29-32 These two histidyl residues are also present in rHb wM and rHb AE and presumably also contribute to the Bohr effect of these proteins." The C terminal residue, 146His, undergoes a pKa shift from about 7.1 to about 8.0 when protonated and in the T state. Briefly explain why the pKa this H residue changes and how this pKa change helps to regulate oxygen delivery to the tissues. (3 pts.) Why or how pKa changes How oxygen delivery is affected: How this His functions to help regulate 02 delivery:

Explanation / Answer

The pKa of an amino acid can be modulated by its microenvironment. The pKa of many amino acids in free solution is different from their pKa when they are present at an enzyme's active site. This because amino acids are affected by solvent molecules only when they are in solution. However, the local microenvironment at the catalytic site has a larger effect on the protonation status of an amino acid.

For example, an acidic amino acid present in a hydrophobic patch resists proton release to become charged.
If an acidic amino acid present adjacent to a basic amino acid readily releases a proton and becomes charged.
pK of an amino acid is also affected by temperature.

Hemoglobin's affinity for oxygen is sensitive to minute changes in pH. This is because His at the Hb active site are charged at lower pH hence decreasing BPG binding. BPG helps in oxygen delivery to muscle cells by promoting the affinity of myoglobin to oxygen.

The binding of oxygen to the Fe-core in Hb exhibits allostery. Binding of the first oxygen molecule to Hb causes a shift in His position towards porphyrin structure which changes the overall conformation of Hb. This changed conformation exhibits increased binding affinity for incoming oxygen molecules.

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