A type 1 diabetic patient uses insulin aspart as part of a basal-bolus regimen. Insulin aspart achieves its rapid onset of action compared to regular human insulin because of which structural modification?
- A Substitution of proline at B28 with aspartic acid, reducing self-association into dimers/hexamers ✓
- B Addition of zinc to form stable hexamers
- C Conjugation with a fatty acid chain binding albumin
- D Removal of the C-peptide from the insulin molecule
Correct answer: A. Substitution of proline at B28 with aspartic acid, reducing self-association into dimers/hexamers
Explanation
Insulin aspart has proline at position A28 replaced by aspartic acid. This negative charge repulsion prevents dimer and hexamer formation, allowing rapid absorption as monomers after subcutaneous injection. Option B would slow absorption. Option C describes insulin detemir/degludec. Option D is irrelevant to pharmacokinetics.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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