Amino Acids & Proteins MCAT Practice Question
A 68-year-old man with progressive memory loss and cognitive decline is found to have amyloid-beta (Aβ) plaques on autopsy. Researchers studying his brain tissue measure the pH in different regions and note that areas with abundant plaque formation have a local pH of 4.5, while surrounding normal tissue maintains a pH of 7.4. In vitro studies show that synthetic Aβ peptides aggregate much more readily at pH 4.5 than at pH 7.4. The Aβ peptide contains multiple histidine residues (pKa ~6.0) and several acidic amino acids (aspartate and glutamate). Which of the following best explains the enhanced aggregation of Aβ at the lower pH observed in plaque-rich regions?
Answer choices
- AProtonation of histidines increases positive charge, but electrostatic repulsion between negatively charged residues is strengthened, preventing aggregation
- BThe acidic amino acids become protonated and neutral, reducing the net negative charge and decreasing electrostatic repulsion between peptide moleculesCorrect answer
- CHistidine residues are fully protonated and impart a strongly positive charge that cross-links peptides through ionic interactions with the negatively charged backbone
- DLow pH causes hydrolysis of peptide bonds in the amyloid-beta backbone, producing smaller fragments that aggregate more easily due to increased solubility
- EDecreased pH denatures the Aβ peptide, exposing hydrophobic core residues that drive aggregation through hydrophobic interactions
- FAcidic pH activates endogenous proteases that cleave Aβ into smaller fragments prone to β-sheet formation
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