Question

Which amino acid is substituted in sickle cell anaemia?

• A. Glutamic acid by valine in α-chain
• B. Glutamic acid by valine in β-chain
• C. Valine by glutamic acid in β-chain
• D. Valine by glutamic acid in α-chain

Answer 1

Answer:

B. Glutamic acid by valine in β-chain

Molecular Basis of Sickle Cell Anaemia

• Sickle cell anaemia is an autosomal recessive genetic disorder caused by a point mutation in the HBB gene, which encodes the beta-globin chain of haemoglobin.
• The mutation occurs specifically at the sixth codon of the beta-globin gene, where a single nucleotide substitution (GAG to GUG) leads to the replacement of the amino acid Glutamic acid with Valine at the sixth position.
• This substitution changes the biochemical properties of the haemoglobin molecule:
  • Glutamic acid is a polar, hydrophilic amino acid.
  • Valine is a non-polar, hydrophobic amino acid.
• The hydrophobic valine residue creates a 'sticky' patch on the surface of the beta-globin chain, causing haemoglobin molecules to polymerize and form long, rigid fibers under low oxygen conditions.
• These fibers distort the shape of the red blood cells from a normal biconcave disc into a characteristic sickle or crescent shape.
• Clinical Significance: The sickled cells are rigid and fragile, leading to:
  • Haemolysis: Premature destruction of red blood cells, resulting in chronic anaemia.
  • Vaso-occlusion: The irregular shape causes cells to clump and block small blood vessels (capillaries), leading to tissue ischemia, severe pain crises, and organ damage.
• Malaria Resistance: Individuals with sickle cell trait (heterozygous condition) possess a significant survival advantage in regions where malaria is endemic, as the parasite Plasmodium falciparum has difficulty infecting and reproducing within sickled red blood cells.