Abnormal Hemoglobin

Question 1

Explain how sickle cell disease can develop anemia

Answer 1

1. HbA (2 alpha, 2 beta chains) is low
2. HbS levels are high
3. Here, polar glutamic acid residue at position six is replaced by non-polar valine residue
4. This generates a hydrophobic ‘sticky patch’ on the surface of the beta chain
5. In hypoxia, leucine + phenylalanine of beta chain, generates hydrophobic pockets and joins with the ‘sticky patch’
6. This leads to polymerization of deoxyHbS inside RBCs and forms a gel. Then assembles to a fibrous network
7. Stiffens & distorts the cell into a sickle shape
8. These block blood flow in small capillaries
9. Makes patient susceptible to intravascular hemolysis leading to anemia

Question 2

What is the genetic basis of sickle cell hemoglobin?

Answer 2

1. Autosomal recessive
2. 2 defective beta globin chain forming genes in chromosome 11

Question 3

Sickle cell hemoglobin vs. Adult hemoglobin

Answer 3

Sickle cell Hb:
1. Polar glutamic acid is replaced by non-polar valine @ position 6 of beta globin chain
2. Generates hydrophobic ‘sticky patch’
3. In low PO2 beta global chains aggregate
4. Insoluble elongated files are formed

Adult Hb:
1. No ‘sticky patch’
2. Do not aggregate

Question 4

Explain how sickle cell anemia offers an advantage against Malaria

Answer 4

1. Due to abnormal shape; lifespan is shortened
2. Malaria is acquired by the parasite plasmodium falciparum.
3. Part of its lifecycle occurs in RBC
4. As sickle shaped cells undergo lysis in a shorter period, the parasite is unable to complete its life cycle
5. Patients have a lower tendency to acquire malaria

Question 5

Explain the biochemical basis of beta thalassemia

Answer 5

1. ↓HbA; ↑HbA2; ↑HbF
2. At chromosome 11, it consists of 2 genes for beta globin chain synthesis
3. Separate genes for gamma globin chains & delta globin chains
4. Beta thalassemia occurs due to hereditary persistence of Hb F for prolonged time even after birth, due to a genetic mutation in gamma -globin synthesizing genes
5. After birth, these genes are inactivated and only beta chainis synthesized. But due to incomplete inactivation of gamma genes, synthesis of adequate beta chains is impaired
6. HbA consists of alpha2beta2 composition; there is no defect in synthesis of alpha chain
7. Due to ↓ beta, delta chains are produced more in order to compensate
8. } Beta thalassemia has occurred due to genetic mutations & ↓ HbA levels