The Effect of CO2 and H+ on O2 Binding
In 1904, Christian Bohr discovered that increased concentrations of CO2 and H+ promote the release of O2 from hemoglobin in the blood. This phenomenon, known as the Bohr effect, is a highly adaptive feature of the body's blood-gas exchange mechanism. The blood that is pumped from the heart to the body tissues and organs (other than the lungs) is rich in oxygen (Figure 7). These tissues require oxygen for their metabolic activities (e.g., muscle contraction). Hence, it is necessary for oxygen to remain bound to hemoglobin as the blood travels through the arteries (so that it can be carried to the tissues), but be easily removable when the blood passes through the capillaries feeding the body tissues. CO2 and H+ are produced from metabolic activities of the body, and so the concentration of these species is high in the metabolically active tissues of the body. Thus, the tissues that perform the most metabolic activity (and therefore require the largest amount of O2) produce large quantities of CO2 and H+, facilitating the release of O2 from the blood where the O2 is most needed. In the lungs, the reverse effect occurs: high concentrations of O2 cause the release of CO2 from hemoglobin.
How do CO2 and H+ promote the release of O2 from hemoglobin? These species help form interactions between amino-acid residues at the interfaces of the four subunits in hemoglobin. These interactions are called "salt bridges," because they are between positively-charged and negatively-charged amino-acid residues on different subunits of the same protein (Figure 8). When "salt bridges" form, the subunits are held in a position that "tugs on" the histidine that is attached to the heme iron. (See Figure 5.) This favors the domed configuration, which is the deoxygenated form of hemoglobin.
When the concentration of protons (H+) is low (pH 9), positive charges do not form on the residues at the subunit interfaces, so the salt bridges cannot form (right image in Figure 8). However, at pH 7, histidine residues at the subunit interfaces (not the histidine residues that bind the heme groups) can accept an additional proton (H+), and hence become positively charged (Equation 1). When salt bridges form by the interaction of these interfacial histidine residues and nearby negatively-charged amino-acid residues, the deoxygenated hemoglobin structure is favored, and oxygen is released (left image in Figure 8).
The number of negatively-charged residues in the salt bridges is increased in the presence of carbon dioxide. CO2 binds to the amino (-NH2) group of certain amino acid residues at the subunit interfaces to produce a negatively-charged group (-NHCOO-) on the residue (Equation 2). This negatively-charged group can form salt bridges with the positive charges on the protonated histidines described above. The H+ produced by Equation 2 can also be accepted by histidine residues at the subunit interfaces (via Equation 1).
Thus, hemoglobin's biological function is regulated by the changing of the overall protein structure. This structure is altered by the binding or releasing of CO2 and H+ to the interfaces of the subunits in hemoglobin (Figure 8).
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This page created by Matt Traverso, Washington University in St Louis.
© 2004, Washington University.
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