Consisting of more than one polypeptide chain, hemoglobin has quaternary structure. Hemoglobin possesses four polypeptide chains attached to an iron containing heme group, a structure for the cooperative binding of oxygen. Subject to the oxygen dissociation curve, hemoglobin takes up O2 in the lungs, where PO2 is high, and releases it in the tissues, where PO2, is low. Binding of oxygen to hemoglobin is cooperative. The first binding brings about an allosteric change in the protein making the next binding occur more easily. Oxygen binding is also affected by blood pH (lower pH = more H+ = lower oxygen affinity) and the presence of certain organophosphate compounds (BPG) (more BPG = lower oxygen affinity).

CO2 reacts with water in the blood to form carbonic acid, leading to a lowering of blood pH. This acidity shifts the oxygen dissociation curve of hemoglobin to the right, the Bohr effect, which causes more oxygen to be delivered to the tissues, where pCO2 is high. In the lungs, when hemoglobin binds oxygen, it gives up its hydrogen ions, which recombine with bicarbonate ion leading to the production of CO2. CO2 can be transported in the blood as HCO3- formed either by slow reaction with water in the blood plasma or by fast reaction in the erythrocyte through the enzyme activity of carbonic anhydrase. Some CO2 travels bound to hemoglobin as carbamino hemoglobin. Some small amount travels as dissolved gas. Reactions in the tissues where CO2 is taken up are reversed in the lungs. Breathing speeds up if blood pH is getting too low.

Many passages on this material have been on the MCAT over the years.