Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 2000 Jul;79(1):406–415. doi: 10.1016/S0006-3495(00)76302-8

Specific binding of ethanol to cholesterol in organic solvents.

V A Daragan 1, A M Voloshin 1, S V Chochina 1, T N Khazanovich 1, W G Wood 1, N A Avdulov 1, K H Mayo 1
PMCID: PMC1300944  PMID: 10866966

Abstract

Although ethanol has been reported to affect cholesterol homeostasis in biological membranes, the molecular mechanism of action is unknown. Here, nuclear magnetic resonance (NMR) spectroscopic techniques have been used to investigate possible direct interactions between ethanol and cholesterol in various low dielectric solvents (acetone, methanol, isopropanol, DMF, DMSO, chloroform, and CCl(4)). Measurement of (13)C chemical shifts, spin-lattice and multiplet relaxation times, as well as self-diffusion coefficients, indicates that ethanol interacts weakly, yet specifically, with the HC-OH moiety and the two flanking methylenes in the cyclohexanol ring of cholesterol. This interaction is most strong in the least polar-solvent carbon tetrachloride where the ethanol-cholesterol equilibrium dissociation constant is estimated to be 2 x 10(-3) M. (13)C-NMR spin-lattice relaxation studies allow insight into the geometry of this complex, which is best modeled with the methyl group of ethanol sandwiched between the two methylenes in the cyclohexanol ring and the hydroxyl group of ethanol hydrogen bonded to the hydroxyl group of cholesterol.

Full Text

The Full Text of this article is available as a PDF (152.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avdulov N. A., Chochina S. V., Daragan V. A., Schroeder F., Mayo K. H., Wood W. G. Direct binding of ethanol to bovine serum albumin: a fluorescent and 13C NMR multiplet relaxation study. Biochemistry. 1996 Jan 9;35(1):340–347. doi: 10.1021/bi9513416. [DOI] [PubMed] [Google Scholar]
  2. Avdulov N. A., Chochina S. V., Igbavboa U., Warden C. S., Schroeder F., Wood W. G. Lipid binding to sterol carrier protein-2 is inhibited by ethanol. Biochim Biophys Acta. 1999 Jan 29;1437(1):37–45. doi: 10.1016/s0005-2760(98)00178-7. [DOI] [PubMed] [Google Scholar]
  3. Avdulov N. A., Wood W. G., Harris R. A. Effects of ethanol on structural parameters of rat brain membranes: relationship to genetic differences in ethanol sensitivity. Alcohol Clin Exp Res. 1994 Feb;18(1):53–59. doi: 10.1111/j.1530-0277.1994.tb00880.x. [DOI] [PubMed] [Google Scholar]
  4. Barry J. A., Gawrisch K. Effects of ethanol on lipid bilayers containing cholesterol, gangliosides, and sphingomyelin. Biochemistry. 1995 Jul 11;34(27):8852–8860. doi: 10.1021/bi00027a037. [DOI] [PubMed] [Google Scholar]
  5. Chin J. H., Goldstein D. B. Effects of low concentrations of ethanol on the fluidity of spin-labeled erythrocyte and brain membranes. Mol Pharmacol. 1977 May;13(3):435–441. [PubMed] [Google Scholar]
  6. Colles S., Wood W. G., Myers-Payne S. C., Igbavboa U., Avdulov N. A., Joseph J., Schroeder F. Structure and polarity of mouse brain synaptic plasma membrane: effects of ethanol in vitro and in vivo. Biochemistry. 1995 May 2;34(17):5945–5959. doi: 10.1021/bi00017a024. [DOI] [PubMed] [Google Scholar]
  7. Daragan V. A., Kloczewiak M. A., Mayo K. H. 13C nuclear magnetic resonance relaxation-derived psi, phi bond rotational energy barriers and rotational restrictions for glycine 13C alpha-methylenes in a GXX-repeat hexadecapeptide. Biochemistry. 1993 Oct 12;32(40):10580–10590. doi: 10.1021/bi00091a007. [DOI] [PubMed] [Google Scholar]
  8. Holte L. L., Gawrisch K. Determining ethanol distribution in phospholipid multilayers with MAS-NOESY spectra. Biochemistry. 1997 Apr 15;36(15):4669–4674. doi: 10.1021/bi9626416. [DOI] [PubMed] [Google Scholar]
  9. Klemm W. R. Biological water and its role in the effects of alcohol. Alcohol. 1998 Apr;15(3):249–267. doi: 10.1016/s0741-8329(97)00130-4. [DOI] [PubMed] [Google Scholar]
  10. Klemm W. R., Williams H. J. Amphiphilic binding site of ethanol in reversed lipid micelles. Alcohol. 1996 Mar-Apr;13(2):133–138. doi: 10.1016/0741-8329(95)02024-1. [DOI] [PubMed] [Google Scholar]
  11. Mayo K. H., Ilyina E., Park H. A recipe for designing water-soluble, beta-sheet-forming peptides. Protein Sci. 1996 Jul;5(7):1301–1315. doi: 10.1002/pro.5560050709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mitchell D. C., Litman B. J. Effect of ethanol on metarhodopsin II formation is potentiated by phospholipid polyunsaturation. Biochemistry. 1994 Nov 1;33(43):12752–12756. doi: 10.1021/bi00209a004. [DOI] [PubMed] [Google Scholar]
  13. Nambi P., Rowe E. S., McIntosh T. J. Studies of the ethanol-induced interdigitated gel phase in phosphatidylcholines using the fluorophore 1,6-diphenyl-1,3,5-hexatriene. Biochemistry. 1988 Dec 27;27(26):9175–9182. doi: 10.1021/bi00426a015. [DOI] [PubMed] [Google Scholar]
  14. Rigby A. C., Barber K. R., Shaw G. S., Grant C. W. Transmembrane region of the epidermal growth factor receptor: behavior and interactions via 2H NMR. Biochemistry. 1996 Sep 24;35(38):12591–12601. doi: 10.1021/bi9611063. [DOI] [PubMed] [Google Scholar]
  15. Rostand K. S., Esko J. D. Cholesterol and cholesterol esters: host receptors for Pseudomonas aeruginosa adherence. J Biol Chem. 1993 Nov 15;268(32):24053–24059. [PubMed] [Google Scholar]
  16. Seeman P. The membrane actions of anesthetics and tranquilizers. Pharmacol Rev. 1972 Dec;24(4):583–655. [PubMed] [Google Scholar]
  17. Villalaín J. Location of cholesterol in model membranes by magic-angle-sample-spinning NMR. Eur J Biochem. 1996 Oct 15;241(2):586–593. doi: 10.1111/j.1432-1033.1996.00586.x. [DOI] [PubMed] [Google Scholar]
  18. Wood W. G., Gorka C., Schroeder F. Acute and chronic effects of ethanol on transbilayer membrane domains. J Neurochem. 1989 Jun;52(6):1925–1930. doi: 10.1111/j.1471-4159.1989.tb07278.x. [DOI] [PubMed] [Google Scholar]
  19. Wood W. G., Rao A. M., Igbavboa U., Semotuk M. Cholesterol exchange and lateral cholesterol pools in synaptosomal membranes of pair-fed control and chronic ethanol-treated mice. Alcohol Clin Exp Res. 1993 Apr;17(2):345–350. doi: 10.1111/j.1530-0277.1993.tb00773.x. [DOI] [PubMed] [Google Scholar]
  20. Wood W. G., Schroeder F., Hogy L., Rao A. M., Nemecz G. Asymmetric distribution of a fluorescent sterol in synaptic plasma membranes: effects of chronic ethanol consumption. Biochim Biophys Acta. 1990 Jun 27;1025(2):243–246. doi: 10.1016/0005-2736(90)90103-u. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES