5.3 Bohr Effect

When O₂ is consumed by body tissues, CO₂ is produced and must be transported back to the lungs to be exhaled out the body.

Figure 5.13: Oxygen Binding Curves

The ability of hemoglobin to release O₂ is enhanced by the CO₂-rich environment of the tissue. This is because the O₂-binding affinity for hemoglobin is reduced as pH drops (see 5.13); the T state of hemoglobin is favored in acidic solutions and the reaction (5.1) occurs:

\[\begin{equation} Hb-4O_2 + nH^+ \leftrightarrow Hb-nH^+ + 4O_2 \tag{5.1} \end{equation}\]

Note that the pH in tissues is far lower than the pH in the lungs - this is because of the reaction (5.2) catalyzed by the enzyme carbonic anhydrase:

\[\begin{equation} CO_2 + H_2O \leftrightarrow H^+ + HCO_3^- \tag{5.2} \end{equation}\]

Furthermore, the uptake of protons in equation (5.1) also help drives equation (5.2) to the right, hence allowing more CO₂ to freely move through the bloodstream.

The above is called the Bohr effect and is vital for the removal of CO₂ as a waste product. In the lungs, the effect works in reverse: the R state of hemoglobin is favored. Protons are shed and reaction (5.2) is driven left to expel CO₂ from the lungs.

5.3.1 Stabilization of the T state

Figure 5.14: Amino Acid Pairs in the T State of Hemoglobin

A major contribution to the Bohr effect is made by the His146 (i.e., His HC3) of the \(\beta\) subunits of hemoglobin.

In the T state (i.e., the protonated state), the His146 residue forms an ion pair with Asp91 (as seen in figure 5.14), hence stabilizing the deoxy form. However, the His146-Asp91 ion pair is unable to form in the R state as the amino acid pairs rotate toward the center of hemoglobin.

5.3.2 CO₂ transport by hemoglobin

Figure 5.15: Carbon Dioxide Transport by Hemoglobin

Hemoglobin is also able to directly transport some CO₂. The high concentration of CO₂ promotes its reaction with the N-terminal residues of hemoglobin to form carbamino groups (see 5.15). The carbamino residues then further stabilize the T state of hemoglobin via ion pairing interactions (hence promoting additional O₂ release).