How does protonation of the histidine group in hemoglobin affect its ability to bind oxygen?

When histidine is protonated, it participates in the regulation of hemoglobin's oxygen-binding properties by influencing its conformation. In the context of hemoglobin, protonation of histidine leads to a more positively charged environment, which can stabilize the T (tense) state of hemoglobin. This T state has a lower affinity for oxygen compared to the R (relaxed) state, which is the conformation that binds oxygen more effectively.

The physiological implication of this behavior is tied to the Bohr effect, where increased levels of carbon dioxide (a metabolic byproduct) and lowered pH (which indicates higher concentrations of protons) shift hemoglobin towards the T state. This reduced affinity for oxygen in tissues that are actively metabolizing glucose (and thus producing CO2 and H+) facilitates oxygen release where it is needed most. Therefore, when histidine gets protonated, it indeed diminishes hemoglobin's binding efficiency for oxygen, aligning with physiological needs during cellular respiration.

This is why the decrease in oxygen binding capacity is a critical aspect of hemoglobin's functionality, allowing it to effectively respond to the demands of oxygen delivery in the body.