Anyone who goes from a long period of inactivity to vigorous exercise (for example, from months of watching television to several hours of racquetball) experiences stiffness due to the buildup of lactic acid
in the tissues. Even during moderate exercise, muscle activity generates the weak acid carbon dioxide. For example, if glucose is oxidized to water and carbon dioxide and the enzyme carbonic anhydrase
interconverts CO 2
and carbonic acid:
The net effect is a drop in pH due to metabolism.
A decrease in pH increases the P 50 of hemoglobin. This phenomenon is called the Bohr effect. Because of the Bohr effect, more O 2 is released from hemoglobin to the tissues where it is needed than would be predicted from simple equilibrium effects. Conversely, in the lungs, where CO 2 leaves the bloodstream by diffusion, the pH increases relative to that in venous blood, and hemoglobin binds oxygen more tightly.
Because heat is a product of metabolism, more oxygen needs to be delivered to the tissues when metabolism is very active, for example during vigorous exercise. Hemoglobin binds oxygen less tightly at higher temperature so that it gives up its oxygen more readily when it is needed.
BPG is a byproduct of glucose metabolism; its structure is shown in Figure 6–4. There is approximately one molecule of BPG per hemoglobin tetramer in the red blood cell. BPG is an allosteric regulator; it binds to a specific site on hemoglobin and shifts the dissociation curve to the left. This means that oxygen is delivered more readily to the tissues. BPG levels increase as an adaptation to high altitude (for example, on moving from Seattle at sea level to Denver at an altitude of 1,700 meters), allowing physical activity under low oxygen conditions. At still higher altitudes, where the pO 2 is lower still, BPG limits the ability of the hemoglobin to bind oxygen in the lungs. This may limit long‐term human activity to altitudes below 5,000 meters above sea level— humans simply can't get enough oxygen into their hemoglobin if the pO 2 is lower than that found at that level.