The metal coordination environment of heme non-catalytic subunits of hemoglobin plays a crucial role in the oxygen binding affinity, especially at high altitudes. Hemoglobin is a tetrameric protein composed of two alpha and two beta subunits, each containing a heme group with an iron Fe atom at its center. The iron atom is responsible for binding to oxygen molecules.At high altitudes, the atmospheric pressure is lower, which results in a decreased partial pressure of oxygen pO2 . This makes it more challenging for hemoglobin to bind to oxygen and deliver it to tissues. The metal coordination environment of heme non-catalytic subunits can affect the oxygen binding affinity of hemoglobin in several ways:1. Coordination geometry: The iron atom in the heme group is coordinated to a nitrogen atom from the imidazole ring of a histidine residue in the protein chain. This histidine residue is called the proximal histidine. The coordination geometry of the iron atom can change from a high-spin to a low-spin state upon oxygen binding. This change in coordination geometry affects the overall conformation of the hemoglobin molecule, promoting the transition from a low-affinity T-state tense to a high-affinity R-state relaxed .2. Allosteric regulation: Hemoglobin exhibits cooperative binding of oxygen, meaning that the binding of one oxygen molecule to a heme group increases the affinity of the remaining heme groups for oxygen. This cooperativity is due to allosteric interactions between the subunits. Changes in the metal coordination environment of heme non-catalytic subunits can affect these allosteric interactions, altering the oxygen binding affinity of hemoglobin.3. Bohr effect: The oxygen binding affinity of hemoglobin is also influenced by the pH and the concentration of carbon dioxide CO2 in the blood. This phenomenon is known as the Bohr effect. At high altitudes, the increased ventilation rate leads to a decrease in blood CO2 levels and an increase in blood pH. These changes can affect the metal coordination environment of heme non-catalytic subunits, resulting in an increased oxygen binding affinity of hemoglobin.4. 2,3-Bisphosphoglycerate 2,3-BPG binding: 2,3-BPG is a small molecule that binds to hemoglobin and decreases its oxygen binding affinity. This effect is particularly important at high altitudes, where the oxygen availability is low. The binding of 2,3-BPG to hemoglobin is influenced by the metal coordination environment of heme non-catalytic subunits. Changes in this environment can modulate the interaction between hemoglobin and 2,3-BPG, affecting the oxygen binding affinity.In summary, the metal coordination environment of heme non-catalytic subunits of hemoglobin plays a critical role in modulating the oxygen binding affinity of the protein, particularly at high altitudes. Changes in this environment can affect the coordination geometry, allosteric regulation, Bohr effect, and 2,3-BPG binding, ultimately influencing the ability of hemoglobin to bind and transport oxygen under low oxygen conditions.