Release of carbon dioxide from respiring tissues lowers the oxygen affinity of hemoglobin in two ways.

1. Some of the carbon dioxide becomes bicarbonate,

CO2 + H2O <-> HCO3^- + H+

releasing protons that contribute to the Bohr effect.

2. Some of this bicarbonate is transported out of the erythrocytes and is carried dissolved in the blood serum. A portion reacts directly with hemoglobin, binding to the N-terminal amino groups of the chains to form carbamates, as follows:

The formation of carbamates allows hemoglobin to aid in the transport of CO2 from tissues to lungs or gills. It has two additional effects, too. First, protons released on binding of HCO3^- contribute to the Bohr effect. Second, a negatively charged group is introduced at the N-terminus of the chains. The negatively charged group stabilizes salt bridge formation between and chains, which is characteristic of the deoxy state. Thus, both the latter effect and the lower pH promote oxygen release when CO2 is abundant.

The reverse of the carbamation reaction, which occurs in lungs or gills (where O2 concentration is high, is equally important. Here, the high O2 concentration favors oxygenation and hence the oxy form of the molecule. When this switch occurs, stabilization of the carbamated N-termini is decreased, and CO2 is expelled and expired.

Thus, from Figure 7.1, in the lungs or gills of an animal, O2 is abundant. Oxygenation favors the oxy conformation of hemoglobin, which stimulates the release of CO2. As the blood then travels via arteries into the tissue capillaries, the lower pH and high CO2 concentration favor the deoxy form, promoting O2 release and binding of CO2. Carbon dioxide, both in forming bicarbonate and in reacting with hemoglobin, causes the release of more protons, further stimulating O2 release and CO2 binding.