In sickle cell disease context, which amino acid is hydrophobic?

• A. Glycine
• B. Proline
• C. Glutamic acid
• D. Valine

Answer: (D)

Amino acid properties determine how proteins fold and interact, and hydrophobicity is a key factor in how amino acids behave on a protein’s surface. Valine has a branched, nonpolar side chain, making it hydrophobic and likely to avoid water. In the sickle cell mutation, a hydrophilic, negatively charged glutamic acid on the beta-globin surface is replaced by valine. This creates a hydrophobic patch on hemoglobin S when oxygen is released, promoting abnormal interactions between hemoglobin molecules and causing them to polymerize into fibers. Those fibers deform red blood cells into a sickle shape. The other options either have charged or small polar/neutral characteristics (glutamic acid is hydrophilic; glycine is tiny and not particularly hydrophobic; proline is nonpolar but has a rigid structure that doesn’t explain the same surface interaction).