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Chemical Activity of Cholesterol in Membranes
Abstract
Measurements are reported for the rate constants for the release of cholesterol (and dihydrocholesterol) to beta-cyclodextrin from mixtures with phospholipids in homogeneous monolayers at constant pressure at the air-water interface. In each mixture, it is found that the release rate shows a sharp decrease as the cholesterol concentration in the monolayer decreases through a composition corresponding to the stoichiometry of a cholesterol-phospholipid complex. The stoichiometry of the complex was established previously by the position of a sharp cusp in the thermodynamic phase diagram of each mixture and also by a minimum in average molecular area versus composition measurements. A theoretical model used earlier to account for the phase diagrams predicts the chemical potential and chemical activity of cholesterol in these mixtures. The calculated chemical activity also shows a sharp change at the complex stoichiometry in homogeneous monolayers. The similarities in change of observed release rate and calculated chemical activity are expected from reaction rate theory where the release rate is proportional to the cholesterol chemical activity. The chemical activity of cholesterol as determined by complex formation between some phospholipids and cholesterol in the plasma membrane of cells may serve a regulatory function with respect to intracellular cholesterol transport and biosynthesis.
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The majority of plasma membrane cholesterol forms complexes with other membrane lipids, including sphingomyelin and phospholipids, and is sequestered and inaccessible for intracellular transport.
“Normally, the majority of PM cholesterol forms complexes with other membrane lipids, including sphingomyelin and phospholipids, and is therefore sequestered and inaccessible for intracellular transport (also known as “chemically inactive”)”
From Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b (2021) · cites this paper as Radhakrishnan & McConnell, 2000
Phospholipid acyl chain saturation has profound effects on the accessibility of cholesterol in membranes.
“In addition to sphingomyelin, phospholipid acyl chain saturation has profound effects on the accessibility of cholesterol in membranes (Radhakrishnan & McConnell, 2000; Sokolov & Radhakrishnan, 2010; Lange et al, 2013; Gay et al, 2015; Chakrabarti et al, 2017).”
From Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b (2021) · cites this paper as Radhakrishnan & McConnell, 2000
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Cited by
Sorted by citations
Molecular basis of accessible plasma membrane cholesterol recognition by the GRAM domain of GRAMD1b
Ercan, B., Naito, T., Koh, D. H. Z., Dharmawan, D., & Saheki, Y. (2021) · The EMBO Journal · doi:10.15252/embj.2020106524 · Cited by 132
Midzak, A., & Papadopoulos, V. (2014) · Traffic · doi:10.1111/tra.12177 · Cited by 38
Metadata
- Authors
- Radhakrishnan, A., & McConnell, H. M.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2000-06-17
- Volume
- 39
- Issue
- 28
- Pages
- 8119-8124
- ISSN
- 0006-2960
- 1520-4995
- Cited by
- 154
- References
- 0
- Language
- en
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