MCQ on Hemoglobin Structure and Function: Lecture Notes and MCQs (Biochemistry)

Note: MCQs with answers at the end 

Hemoglobin Structure:

- Hemoglobin is a heme-containing protein of the red blood cells
- Globular proteins with a diameter of 6.4 nm with a molecular weight of 64.5 kDa
- Heterodimers consisting of two α and two  β subunits
- Each subunit consist of a heme pocket that binds to the oxygen
- Heme is a tetrapyrrole ring structure consisting of  Fe+2 at the center
- The α subunit consist of 141 amino acids and the β subunit consists of 146 amino acids
- The hydrophobic interaction of the αβ dimers tightly held the quaternary structure of hemoglobin

Hemoglobin Function

- Hemoglobin is present in the Red Blood Cells (RBCs) and primarily carries oxygen from the lungs to the peripheral tissues
- One hemoglobin binds to four oxygen molecules and shows cooperativity
- Binding of one oxygen to a subunit induces the conformational change to convert T-state to R-state
-The R-state favors the binding of oxygen and facilitates the binding of oxygen to three other subunits.
-The T-state to R-state transition occurs when α1β1 and α2β2 dimers rotate 15-degree relative to its plane after oxygen binding to hemoglobin

Oxygen Saturation/Dissociation and Affinity of Hemoglobin:

-The hemoglobin oxygen dissociation curve is a plot of percent saturation of hemoglobin as a function of the partial pressure of oxygen (pO2)
-The hemoglobin-oxygen dissociation curve is sigmoidal and shows cooperative interaction of hemoglobin-oxygen interaction
At a pO2 of 100 mmHg, hemoglobin is 100% saturated, and oxygen is bound to all four heme of hemoglobin molecules
-At a pO2 of  40 mmHg, hemoglobin is 75% saturated, and approximately, three oxygen is bound to each hemoglobin molecule
-At a pO2 of 25 mmHg, hemoglobin is 50% saturated, and two oxygen is bound to each hemoglobin molecule. The partial pressure of oxygen at which the hemoglobin is 50% saturated is also known as P50. 
-When the partial pressure of oxygen is above P50, the hemoglobin favors binding and sequestration of oxygen
- When the partial pressure of oxygen is below P50, the hemoglobin favors the release of oxygen

Partial Pressure of Oxygen in Lungs and Peripheral Tissues Facilitate the Transport and Delivery of Oxygen

- At high partial pressure of oxygen in the lungs (>>P50), the hemoglobin present in the RBC binds and sequesters oxygen and transport it into the peripheral tissue 
- Once the RBC reaches the peripheral tissues with the low partial pressure of oxygen (<<P50), the hemoglobin favors the dissociation and unloading of oxygen

Allosteric Effectors Hemoglobin:

2-3 Bis phosphoglycerate (2,3-BPG)
- 2, 3 Bis phosphoglycerate is a glycolytic intermediate formed by the isomerization of 1,3 bis phosphoglycerate catalyzed by 2, 3 bis phosphoglycerate mutase in red blood cells.
-2, 3 Bis phosphoglycerate is present in an equimolar concentration (2 uM ) to hemoglobin
- A single 2,3-BPG binds to one hemoglobin at the center pocket present in the T-state hemoglobin (deoxygenated hemoglobin)
- 2,3-BPG decreases oxygen affinity of hemoglobin and shifts the oxygen saturation curve toward the right
- During T-R transition, the pocket collapse and the 2,3 BPG can no longer bind to hemoglobin
- In absence of 2,3-BPG, the purified hemoglobin has high affinity and a similar oxygen saturation curve to that of myoglobin
Hydrogen Ions & carbon dioxide (Bohr Effect)
-The regulation of oxygen binding by hydrogen ions or carbon dioxide is known as the Bohr effect
-Increased hydrogen ion (low pH) decreases the oxygen affinity of hemoglobin, enabling the release of oxygen in the peripheral tissues such as exercising muscle
-Increase in hydrogen ion cause the protonation of the β146 and forms the salt bridge with β94 to stabilize the T-state
-Carbon dioxide stabilizes deoxyhemoglobin by reacting with the N-terminal group to form carbamate groups, which are previously negatively charged and stabilized T-state

Types of Hemoglobin:
Based on the structure and subunit component, the hemoglobin can be classified as
Adult Hemoglobin (HbA): Major form of an adult form of hemoglobin consisting of α2β2 chains

Adult Hemoglobin Minor (HbA2): minor of an adult form of hemoglobin consisting of α2δ2

Fetal Hemoglobin (HbF): Fetal form of hemoglobin that is present in the fetus and consists of  α2γ2 chain. HbF does not bind to the 2.3-BPG and has a higher affinity for oxygen compared to HBA. 
-This facilitates the transport of oxygen from the mother to the fetus 


                          MCQ on Hemoglobin Structure and Function

1. What is the primary function of hemoglobin in the human body?
a) Oxygen transport
b) Carbon dioxide transport
c) Nutrient transport
d) Waste removal

2. Which of the following factors can affect the affinity of hemoglobin for oxygen?
a) Temperature
b) Carbon dioxide
c) pH
d) All of the above

3. How does hemoglobin transport oxygen throughout the body?
a) It carries oxygen dissolved in plasma.
b) It binds to oxygen and releases it in the tissues.
c) It converts oxygen into a soluble form for transportation.
d) It breaks down oxygen into its constituent elements.

4. What is the role of hemoglobin in carbon dioxide transport?
a) It carries carbon dioxide dissolved in plasma. 
b) It breaks down carbon dioxide into its constituent elements.
c) It converts carbon dioxide into a soluble form for transportation.
d) It binds to carbon dioxide and releases it in the lungs.

5. How many heme groups are present in a single hemoglobin molecule?
a) 1
b) 2
c) 4
d) 8

6. Which of the following is inherited blood disorder that causes reduction of normal hemoglobin (Hb) level in the body?
a) Muscular dystrophy
b) Thalassemia
c) Leukemia
d) Hemophilia

7. Which diagnostic test is commonly used to measure hemoglobin levels in the blood?
a) Complete blood count (CBC)
b) Electrocardiogram (ECG)
c) Magnetic resonance imaging (MRI)
d) Urinalysis

8. What is the most common type of anemia found around the world?
a) Vitamin B-12 deficiency anemia
b) Sickle cell anemia
c) Iron-deficiency anemia
d) Leukemia

9. Which of the following hemoglobin (Hb) is the major form of hemoglobin found in adults?
a) HbA
b) HbB
c) HbF
d) HbS

10. Name the hemoglobin produced by the result of sickle cell anemia disorder.
a) HbA
b) HbC
b) HbF
d) HbS

1. a) Oxygen transport
2. d) All of the above
3. b) It binds to oxygen and releases it in the tissues.
4. d) It binds to carbon dioxide and releases it in the lungs.
5. c) 4
6. b) Thalassemia. Normal Hb range is 14-18 g/dl for males and 12-16 g/dl for females.
7. a) Complete blood count (CBC)
8. c) Iron-deficiency anemia
9. a) HbA
10. d) HbS