Molecular Organization of Cholesterol in Unsaturated Phosphatidylethanolamines: X-ray Diffraction and Solid State 2H NMR Reveal Differences with Phosphatidylcholines
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- 作者：Saame Raza Shaikh ; Vadim Cherezov ; Martin Caffrey ; Smita P. Soni ; Daniel LoCascio ; William Stillwell ; and Stephen R. Wassall
- 刊名：Journal of the American Chemical Society
- 出版年：2006
- 出版时间：April 26, 2006
- 年：2006
- 卷：128
- 期：16
- 页码：5375 - 5383
- 全文大小：148K
- 年卷期：v.128,no.16(April 26, 2006)
- ISSN：1520-5126
文摘
The major mammalian plasma membrane lipids are phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and cholesterol. Whereas PC-cholesterol interactions are well studied, far less isknown about those between PE and cholesterol. Here, we investigated the molecular organization ofcholesterol in PEs that vary in their degree of acyl chain unsaturation. For heteroacid sn-1 saturated(palmitoyl), sn-2 unsaturated (various acyl chain) PEs, cholesterol solubility determined by X-ray diffractionwas essentially identical with 1 (oleoyl, 51 ± 3 mol %) and 2 (linoleoyl, 49 ± 2 mol %) double bonds beforedecreasing progressively with 4 (arachidonyl, 41 ± 3 mol %) and 6 (docosahexaenoyl, 31 ± 3 mol %)double bonds. With 6 double bonds in each chain, cholesterol solubility was further reduced to 8.5 ± 1 mol%. However, 2H NMR experiments established that the orientation of cholesterol in the same heteroacidPE membranes was unaffected by the degree of acyl chain unsaturation. A tilt angle of 15 ± 1
wasmeasured when equimolar [3
-2H1]cholesterol was added, regardless of the number of double bonds inthe sn-2 chain. The finding that solubility of cholesterol in sn-1 saturated PEs depends on the amount ofpolyunsaturation in the sn-2 chain of PE differs from the equivalent PCs that universally incorporate ~50mol % sterol. Unlike PCs, a differential in affinity for cholesterol and tendency to drive lateral segregationis inferred between polyunsaturated PEs. This distinction may have biological implications reflected by thehealth benefits of dietary polyunsaturated fatty acids that are often taken up into PE > PC.
wasmeasured when equimolar [3-2H1]cholesterol was added, regardless of the number of double bonds inthe sn-2 chain. The finding that solubility of cholesterol in sn-1 saturated PEs depends on the amount ofpolyunsaturation in the sn-2 chain of PE differs from the equivalent PCs that universally incorporate ~50mol % sterol. Unlike PCs, a differential in affinity for cholesterol and tendency to drive lateral segregationis inferred between polyunsaturated PEs. This distinction may have biological implications reflected by thehealth benefits of dietary polyunsaturated fatty acids that are often taken up into PE > PC.