2,3-Bisphosphoglycerate (2,3-BPG) plays a significant role in regulating haemoglobin's oxygen affinity. It is a byproduct of red blood cells' glycolytic pathway and binds to the central cavity of deoxygenated haemoglobin. The binding of 2,3-BPG stabilizes the Tense (T) state of haemoglobin, making it harder for oxygen to bind. This mechanism is crucial for facilitating oxygen release in tissues. In conditions where tissues require more oxygen, such as high altitudes or anaerobic exercise, the concentration of 2,3-BPG in red blood cells increases. This increase leads to a right shift in the oxyhaemoglobin dissociation curve, enhancing oxygen delivery to tissues. Conversely, a decrease in 2,3-BPG levels leads to a left shift in the curve, increasing haemoglobin's affinity for oxygen. This adaptability of haemoglobin, influenced by 2,3-BPG, is vital for maintaining optimal oxygen levels across various physiological conditions.

The structural changes in haemoglobin during oxygenation and deoxygenation are central to its function. In the deoxygenated state, haemoglobin adopts a Tense (T) state where it has a lower affinity for oxygen. This conformation is stabilized by interactions between the polypeptide subunits and the presence of 2,3-BPG. When oxygen binds to the heme groups, these interactions are disrupted, and haemoglobin undergoes a conformational change to the Relaxed (R) state, which has a higher affinity for oxygen. This change enhances the binding of additional oxygen molecules. Conversely, when haemoglobin releases oxygen in the tissues, it reverts to the T state, facilitating the release of remaining oxygen molecules. This dynamic structural shift is crucial for efficient oxygen uptake in the lungs and release in the tissues.

Haemoglobin can indeed carry gases other than oxygen, most notably carbon dioxide (CO2) and carbon monoxide (CO). Around 20% of CO2 produced in metabolism is carried back to the lungs bound to haemoglobin, but not at the oxygen-binding sites. Instead, CO2 binds to the amino groups of the globin portion of haemoglobin, forming carbaminohaemoglobin. This binding contributes to the Bohr effect, as the CO2 binding lowers haemoglobin's affinity for oxygen, facilitating oxygen release. However, the binding of CO is more problematic. CO binds to the heme groups of haemoglobin with a much higher affinity than oxygen, forming carboxyhaemoglobin. This binding not only prevents oxygen binding but also makes the remaining oxygen-binding sites less likely to release their oxygen. This effect can lead to significant impairment of haemoglobin's oxygen transport capacity, resulting in tissue hypoxia and other severe health issues.

The P50 value is a crucial parameter in understanding haemoglobin's oxygen-binding affinity. It refers to the partial pressure of oxygen (pO₂) at which haemoglobin is 50% saturated with oxygen. Essentially, the P50 value indicates how readily haemoglobin binds to and releases oxygen. A lower P50 value suggests a higher affinity for oxygen, meaning haemoglobin holds onto oxygen more tightly and releases it less easily. Conversely, a higher P50 value implies a lower oxygen affinity, indicating easier oxygen release to tissues. This value can vary among different species, reflecting adaptations to their specific environments. For instance, species in low oxygen environments, like those at high altitudes, often have haemoglobins with lower P50 values, enabling them to efficiently bind oxygen under these conditions. In clinical settings, the P50 value can also provide insight into the oxygenation status of patients and how various factors like pH, CO₂ levels, and temperature are affecting haemoglobin's oxygen-binding capacity.

Carbon monoxide (CO) has a profound impact on haemoglobin's ability to transport oxygen. CO binds to the heme groups in haemoglobin with a much higher affinity than oxygen – approximately 200 times greater. When CO binds to haemoglobin, it forms carboxyhaemoglobin, which not only reduces the amount of oxygen that can be carried but also alters the haemoglobin molecule's shape. This change in shape increases the affinity of the remaining binding sites for oxygen, making it harder for oxygen to be released to body tissues. Consequently, even small amounts of CO can significantly impair the oxygen-carrying capacity of haemoglobin, leading to reduced oxygen delivery to tissues and potentially causing severe health effects such as tissue hypoxia and carbon monoxide poisoning. This effect underlines the importance of avoiding CO exposure, as it can disrupt the critical oxygen transport function of haemoglobin in the blood.