Question

In oxygenated hemoglobin, \(\mathrm{p} K_{4}=6.6\) for the histidines at position 146 on the \(\beta\) -chain. In deoxygenated hemoglobin, the \(p K\) of these residues is 8.2 . How can this piece of information be correlated with the Bohr effect?

Short answer

The higher pK value in deoxygenated hemoglobin allows for increased proton uptake, facilitating oxygen release, aligning with the Bohr effect.

Step-by-step solution

Understand the Bohr Effect

The Bohr effect describes how oxygen binding to hemoglobin decreases with increasing concentration of hydrogen ions (lower pH). Conversely, as the concentration of hydrogen ions decreases (higher pH), hemoglobin binds oxygen more strongly.

Identify the given pK values

For the histidines at position 146 on the β-chain: In oxygenated hemoglobin, \( \text{p}K_4 = 6.6 \) ; In deoxygenated hemoglobin, \( \text{p}K = 8.2 \).

Analyze the pK shift

A shift from pK 6.6 (oxygenated) to pK 8.2 (deoxygenated) indicates that deoxygenated hemoglobin has a higher affinity for hydrogen ions, hence it is more likely to bind protons at a given pH compared to oxygenated hemoglobin.

Correlate with the Bohr Effect

When hemoglobin releases oxygen (deoxygenates), the histidine residues have a higher pK, meaning they will accept more protons, contributing to the increase in proton concentration and thereby facilitating the release of oxygen. This is a key aspect of the Bohr effect.

Key concepts

hemoglobin

Hemoglobin is a protein found in red blood cells responsible for transporting oxygen from the lungs to various body tissues and bringing carbon dioxide back to the lungs to be exhaled. It consists of four subunits, each capable of binding one molecule of oxygen. Each subunit contains an iron-bound heme group essential for oxygen binding.
The precise manner in which hemoglobin binds and releases oxygen is influenced by several factors, including the pH of the blood and the concentration of carbon dioxide, factors closely related to the Bohr effect.

pK values

pK values are a measure of the acidity of specific groups within a molecule, indicating the pH at which a given chemical group is half protonated and half deprotonated. In simpler terms, for a given amino acid residue, the pK value tells us at what pH level it is equally likely to either donate or accept a proton.
In the context of hemoglobin, pK values of certain residues, like histidine, change depending on whether hemoglobin is oxygenated or deoxygenated. This change plays an important role in the protein's ability to bind or release oxygen in response to varying environmental conditions, such as different pH levels.

histidine residues

Histidine residues are specific sites within the hemoglobin molecule that can impact its function due to their unique capability to act as proton acceptors or donors. Histidine is an amino acid with a side chain that includes an imidazole group, which can pick up or release a proton depending on the pH.
In the case given, histidines at position 146 of the β-chain exhibit different pK values in oxygenated (pK = 6.6) versus deoxygenated (pK = 8.2) states. This shift in pK values when hemoglobin changes its state illustrates how histidine's ability to bind protons is altered, which is crucial for the Bohr effect.

oxygen binding

Oxygen binding to hemoglobin is a complex process influenced by several factors including pH, carbon dioxide levels, and the presence of certain molecules like 2,3-Bisphosphoglycerate (2,3-BPG). Hemoglobin undergoes conformational changes between its oxygenated (oxyhemoglobin) and deoxygenated (deoxyhemoglobin) states, each with distinct affinities for oxygen.
When the pH is higher (indicating lower hydrogen ion concentration), hemoglobin binds to oxygen more tightly. Conversely, at a lower pH (higher hydrogen ion concentration), hemoglobin releases oxygen more readily. This relationship ensures that oxygen is efficiently picked up in the lungs and released in the tissues, where it is needed most.

proton concentration

Proton concentration, closely related to the pH level of a solution, significantly impacts hemoglobin's ability to bind or release oxygen. High proton concentration, indicating a low pH, leads to increased protonation of histidine residues, resulting in hemoglobin releasing more oxygen – this is the essence of the Bohr effect.
The shift in pK values for histidine residues at position 146 from 6.6 (oxygenated) to 8.2 (deoxygenated) suggests that deoxygenated hemoglobin has a higher tendency to accept protons, increasing proton concentration within the hemoglobin molecule. This enhanced proton binding promotes the release of oxygen, aiding efficient oxygen transport and delivery.