In sickle cell hemoglobin, which amino acid substitution occurs?

• A. glycine to valine
• B. glutamic acid to valine
• C. valine to glutamic acid
• D. alanine to valine

Answer: (B)

A single amino acid change in the beta-globin chain is enough to alter how hemoglobin behaves. In sickle cell hemoglobin, glutamic acid is replaced by valine at position six of the beta-globin chain. Glutamic acid carries a negative charge and is hydrophilic, while valine is nonpolar and hydrophobic. This substitution removes a charged, water-attracting site and introduces a hydrophobic patch, which promotes abnormal interactions between deoxygenated hemoglobin molecules. Those interactions cause hemoglobin to polymerize and distort red blood cells into a sickle shape, leading to the characteristic symptoms. Other substitutions would be different changes and do not reflect the specific mutation responsible for sickle cell disease.