Amino Acids & Proteins MCAT Practice Question
A 24-year-old man of African descent presents to the emergency department with acute chest pain, dyspnea, and fever. Laboratory studies reveal hemoglobin concentration of 8.2 g/dL and reticulocyte count of 12%. Peripheral blood smear shows sickle-shaped red blood cells. Genetic sequencing confirms a missense mutation in the β-globin gene at codon 6, where glutamic acid is replaced by valine. Which of the following best explains the molecular mechanism by which this amino acid substitution leads to hemoglobin polymerization?
Answer choices
- AGlutamic acid normally stabilizes hemoglobin structure through hydrophobic interactions that valine cannot maintain, causing destabilization and polymerization
- EValine's positive charge creates electrostatic repulsion between hemoglobin molecules, promoting polymerization under deoxygenated conditions
- BValine introduces a hydrophobic residue at the protein surface that mediates polymerization through hydrophobic interactions with complementary patches on adjacent hemoglobin moleculesCorrect answer
- CThe valine substitution prevents formation of a critical disulfide bond required for normal quaternary structure, allowing abnormal hemoglobin cross-linking
- DGlutamic acid normally forms ionic interactions with lysine residues that stabilize the hemoglobin tetramer; valine cannot form these bonds, destabilizing quaternary structure
- FThe loss of glutamic acid's negative charge eliminates a critical interaction with hemoglobin's oxygen-binding pocket, reducing oxygen affinity and promoting sickling
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