An alternative mechanism to preserve O delivery in the face of low ambient oxygen is to increase the affinity of the blood. The oxygen content of the blood is related to PaO and is illustrated using an oxygen equilibrium curve (OEC). Fish hemoglobins, with the exception of the agnathans, are tetramers that exhibit cooperativity of O binding and have sigmoidal OECs.
The binding affinity of hemoglobin to oxygen is estimated using a measurement called P50 (the partial pressure of oxygen at which hemoglobin is 50% bound with oxygen) and can be extremely variable. If the hemoglobin has a weak affinity for oxygen, it is said to have a high P50 and therefore constrains the environment in which a fish can inhabit to those with relatively high environmental PO. Conversely, fish hemoglobins with a low P50 bind strongly to oxygen and are then of obvious advantage when attempting to extract oxygen from hypoxic or variable PO environments. The use of high affinity (low P50) hemoglobins results in reduced ventillatory and therefore energetic requirements when facing hypoxic insult. The oxygen binding affinity of hemoglobin (Hb-O) is regulated through a suite of allosteric modulators; the principal modulators used for controlling Hb-O affinity under hypoxic insult are:
#Increasing RBC pH
#Reducing inorganic phosphate interactions