Question

In plain language, describe what the oxygen-hemoglobin dissociation curve shows. Under normal conditions, the curve can shift to the right and left. A right shift can be induced by increased temperature and lower pH among other things. Describe what a right shift means in terms of hemoglobin’s relationship to oxygen. In your answer, be sure you address what is actually happening at the level of the protein (hemoglobin is a protein). Discuss what types of molecular interactions that can cause a protein to change shape? Does a shape change necessarily mean that the protein denatures? ​

Please answer the questions above based on the paragraph and the diagram down below. Thank you very much!

Sickle cell anemia is a condition in which hemoglobin (Hb) molecules have a single amino acid substitution (glutamic acid switched for valine). Under certain conditions, hemoglobin with this mutation (HB- S) collapses in on itself and polymerizes (attaches) with other hemoglobin molecules resulting in long chains of Hb-S in the red blood cell. As a result, the red blood cell will become brittle and rigid and take on the characteristic "sickle" shape (Fig 1). These cells become sticky and adhere to one another. You are a researcher studying the physiological implications of sickle cell disease, the disease that results when a person is homozygous for the sickle cell gene (meaning they do not have any normal hemoglobin) You are particularly interested in whether hemoglobin with this single mutation has an altered affinity for oxygen.

Answer 1

At higher altitudes, the PO2 decreases, so, breathing an oxygen-enriched gas mixture help keep a person alive at high altitude and also our body makes some adaptations to meet the metabolic oxygen demands. We can observe an increased rate of respiration in people who reached the high altitudes (means, people who are not adapted to that environment).

At normal levels, a high pH, low CO₂, or low 2,3-Bisphosphoglyceric acid (BPG) favors the relaxed form, which can form better binding capacity of oxygen and haemoglobin. The partial pressure of the system also produces a notable affect on O₂ affinity where, at high partial pressures of oxygen (such as those present in the alveoli of the lungs), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, Tau (T state)) tense state is favoured.

The atmospheric pressure of oxygen decreases at high altitudes. One of the key change observed in this adaptation is increased 2,3-BPG (2,3- bisphosphoglycerate), which shift P₅₀ to higher values. 2,3-BPG decreases the oxygen binding affinity of hemoglobin by decreasing its affinity for oxygen due to alteration in conformational changes, oxygen is loosely bound to hemoglobin in the presence of BPG. So, increased levels of 2,3-BPG makes more oxygen available to cells.

According to the Bohr's principle, the oxygen binding affinity of the hemoglobin is inversely proportional to the concentration of carbon dioxide and acidity. The right shift of the oxygen-hemoglobin curve indicates the less affinity of the hemoglobin towards oxygen, in this state, the hemoglobin releases more oxygen to the tissues.

(Hemoglobin stripped of 2,3-BPG) 100г (Normal blood) (High lelves of 2,3-BFG) (Blood from individual adapted to high altitudes) 40 80 120 Partial pressure of oxygen (mm Hg)