Crowding and the polymerization of sickle hemoglobin

✍ Scribed by Frank A. Ferrone; Maria A. Rotter

• Book ID: 102374193
• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 135 KB
• Volume: 17
• Category: Article
• ISSN: 0952-3499
• DOI: 10.1002/jmr.698

✦ Synopsis

Abstract

Under physiological conditions, sickle hemoglobin, a natural mutant of human hemoglobin A with a surface hydrophobic valine in place of a negatively charged glutamic acid, polymerizes at high volume occupancy. Equilibrium solubility of sickle hemoglobin entails activity coefficients that can approach 10^3^ at high concentrations. Polymerization occurs by homogeneous and heterogeneous nucleation mechanisms, which are both profoundly sensitive to crowding; homogeneous nucleation rates for example are enhanced by 10^10^ when the initial concentration is augmented by 50% non‐polymerizing hemoglobin. A molecular description of the reaction therefore entails substantial corrections for molecular crowding which are all very accurately described by excluded volume corrections, treating hemoglobin as a hard sphere with volume consistent with the molecular structure of the molecule, and involving no further adjustable parameters. These effects and the descriptions that rationalize this behavior are described. Copyright © 2004 John Wiley & Sons, Ltd.