RGI.8 Haemoproteins II: Cooperative Oxygen Binding, Allosteric Effects, and Carbon Monoxide Toxicity

Myoglobin (Mb): Myoglobin has a hyperbolic saturation curve, reflecting its high affinity for oxygen and capacity to bind it even at low partial pressures. This property allows myoglobin to effectively store oxygen in muscle tissues for periods of anaerobic respiration.
Haemoglobin (Hb): Haemoglobin exhibits a sigmoidal (S-shaped) curve indicating cooperative binding, meaning that once one oxygen molecule binds, it becomes easier for additional oxygen molecules to bind. This allows for efficient oxygen uptake in the lungs and release in tissues.

At high concentrations of oxygen (such as in the lungs), hemoglobin becomes saturated with oxygen, allowing effective transport to tissues. However, in muscle tissues where oxygen concentration is lower, hemoglobin releases oxygen through cooperative binding, enhancing oxygen transfer where it is most needed.

Transport of CO2: Haemoglobin returns CO2 from tissues to the lungs, mainly as bicarbonate formed from CO2 and water in erythrocytes via the enzyme carbonic anhydrase. Some CO2 binds to amino groups on hemoglobin as carbamate, facilitating CO2 removal.
Transport of H+: H+ ions generated during metabolism bind to hemoglobin, promoting oxygen release through shifts in the oxygen binding curve (Bohr Effect), enhancing oxygen delivery in more acidic environments (e.g., active muscles).

Cooperative binding refers to the phenomenon where binding of one oxygen molecule to hemoglobin enhances the binding of additional oxygen molecules. In hemoglobin, this is facilitated by conformational changes in the protein as the first oxygen binds, destabilizing the T state (tense) and leading to a transition to the R state (relaxed), which has a higher affinity for oxygen.

Allosteric effects occur when the binding of a molecule at one site on a protein affects the binding properties at a different site. In hemoglobin, the binding of oxygen (an allosteric effector) affects the binding of further oxygen molecules, as well as the binding of H+ and CO2, contributing to enhanced physiological efficiency.

The Bohr Effect describes how increased levels of CO2 and H+ (lower pH) in tissues lead to a rightward shift in the oxygen saturation curve of hemoglobin. This means hemoglobin releases more oxygen in acidic conditions, which often corresponds with high metabolic activity in tissues, effectively facilitating oxygen delivery where it is needed most.

Carbon monoxide (CO) is toxic because it competes with oxygen for binding sites on hemoglobin. CO binds with an affinity 225 times greater than that of oxygen, forming carbonmonoxyhemoglobin, which prevents oxygen transport and leads to hypoxia. CO binding also inhibits normal oxygen release in tissues, exacerbating oxygen deprivation.

Haemoglobin has a much higher affinity for CO compared to O2 (225 times greater), resulting in significant risk during CO exposure. Myoglobin also has an increased affinity for CO, approximately 25 times greater than for O2. This strong binding means CO can displace oxygen from both hemoglobin and myoglobin, leading to reduced oxygen availability in tissues and potentially resulting in fatal outcomes without intervention.