- There is an important adaptation that occurs with red blood cells in higher altitudes. 
- At sea level altitudes the arterial vs venous pO2 or the oxygen pressure is significantly different and hemoglobin releases 38% of its bound oxygen.
- There is an increase in BPG at higher altitudes which causes the curve to shift to the right because there is a lower affinity for oxygen.
- However in the higher altitudes starting around 4500m, hemoglobin can only drop off 30% of its oxygen. 
- Thus, in higher-altitudes the amount of oxygen that binds to the hemoglobin is less but the amount of oxygen released is more. 

Blood Oxygen Levels and high Altitudes

- There are additional compounds in the blood stream that effect the oxygen levels besides CO2
- The compound 2,3-bisphosphoglycerate (BPG) binds to deoxyhemoglobin (empty O2 bound hemoglobin) 
- BPG in blood decreases the oxygen affinity by keeping hemoglobin in the deoxyhemoglobin conformation. 
- In the absence of BPG, O2 would not release from the hemoglobin.

Grand Valley State University

- Tetramer of myoglobin-like polypeptides (dimer of alpha beta subunits)
- Delivers oxygen to tissues throughout the body.
- Once oxygen binds, structural change causes oxygen binding affinity to grow in the three other binding sites
- Hemoglobin has two conformation states:
  - T-state
  - R-state


Hemoglobin

Voet, D., Voet, J. G., & Pratt, C. W. (2013). Chapter 7: Protein Function: Myoglobin and Hemoglobin, Muscle Contractions, and Antibodies. In Fundamentals of biochemistry: Life at the molecular level (4th ed., pp. 176-216). Hoboken, NJ: Wiley. Retrieved February 21, 2021, from archive.org.

Fundamental of biochemistry: Life of the molecular level 4th edition: Chapter 7

- A flat ring that contains an iron atom in the center that binds the oxygen atom in a reversible reaction to be able to release oxygen.
- The heme group binds to myoglobin 
- Heme binds four times to hemoglobin 
- Oxygenation of heme causes hemoglobin to change color from dark purple to a scarlet color. 
- In addition to oxygen, however, it can bind things like NO, CO, and H2S and they bind to a higher affinity than oxygen which is evidence of the toxicity of CO.
- CO has a 200-fold greater affinity for hemoglobin than oxygen. 

Heme

- The hemoglobin curve has a sigmoidal (S-shaped) curve instead of the hyperbolic curve for myoglobin.
- Cooperative interaction between the binding sites is displayed, because once a single oxygen binds to hemoglobin the affinity for oxygen at the other sites increases affinity for oxygen at the other subunits. 
- As more oxygen atoms bind to hemoglobin, the slope of the curve increases. 
- Hemoglobin is more saturated with oxygen in arterial oxygen pressures and in venous oxygen pressures hemoglobin is only about half saturated with oxygen. 
- Additionally, the background indicates the color change that occurs with oxygen binding to hemoglobin (blue to red). 


Hemoglobin binding curve

There are many diseases associated with mutations in hemoglobin.
- Sickle-cell anemia 
- Polycythemia 
- Cyanosis
- Hemolytic anemia

Mutations in hemoglobin

2,3-bisphosphoglycerate (BPG)

-  The T-state is the hemoglobin conformational state of deoxyhemoglobin, or the hemoglobin without oxygen bound.
- The iron is situated 6 Angstroms out of the heme and allows for the iron to access oxygen. 


T-State of Hemoglobin

- R-state is the conformational state of oxyhemoglobin.
- When oxygen binds, it “flattens” the iron complex. 
- To prevent steric clash during flattening of the heme, there is an alpha helix that tilts as well.
- Overall, changes in hemoglobin's conformational states at the tertiary level cannot occur without causing quaternary structure changes in the whole protein. 

Learn Before

Related

Learn After