Role of cholesterol in membranes effects on phospholipid-protein interactions, membrane permeability and enzymatic activity

doi:10.1016/0005-2736(73)90280-0

Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume 330, Issue 1, 30 November 1973, Pages 8-26

https://doi.org/10.1016/0005-2736(73)90280-0 Get rights and content

Abstract

The effect of cholesterol on the interaction of proteins with phospholipid membranes was studied using three independent techniques: effects on vesicle permeability, monolayer expansion, and phospholipid-dependent (Na⁺ + K⁺)-ATPase activity. The proteins studied were: cytochrome c, albumin, hemoglobin, lysozyme, myelin basic protein, myelin proteolipid apoprotein, and the polypeptide gramicidin A. The results were as follows:

1.
1. All the proteins in this study produced a large increase in the permeability of phospholipid vesicles to Na⁺. When cholesterol was mixed with phospholipid in equimolar proportions, most proteins produced only a comparatively small increase in permeability. This inhibitory effect of cholesterol on the permeability of phospholipid-protein membranes, was 38-fold for cytochrome c and 10-fold for hemoglobin. The only protein that was not affected by cholesterol was the myelin proteolipid apoprotein. Experiments with cytochrome c indicated that the above effects were unlikely to be due to inhibition of its binding to phosphatidylserine vesicles.
2.
2. The presence of cholesterol in phosphatidylserine monolayers inhibits the area expansion produced by the addition of cytochrome c to the bulk phase. The inhibition of monolayer expansion by cholesterol was shown to be considerably larger than that obtained by equivalent dilution of the surface charges of phosphatidylserine by phosphatidylcholine.
3.
3. The presence of cholesterol inhibits the ability of phospholipids to activate a delipidated preparation of (Na⁺ + K⁺)-ATPase. The degree of inhibition produced by nearly equimolar mixtures of cholesterol with brain phosphatidylserine and dioleylphosphoatidylglycerol was approximately 60% while in mixtures with dipalmitoylphosphatidylglycerol, it was more than 90%.
4.
4. The biological significance of these data are discussed in relation to the possible effects of increased cholesterol levels in cell membranes during the process of aging and the development of atherosclerosis.

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Role of cholesterol in membranes effects on phospholipid-protein interactions, membrane permeability and enzymatic activity

Abstract

FEBS Lett.

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FEBS Lett.

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