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Modeling Cholesterol in Humans: Update and Dealing with the Problem of Exchange in Vivo Using the Blood Cell-Lipoprotein Paradigm

  • Charles C. Schwartz
  • Julie M. VandenBroek
  • Patricia S. Cooper
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 537)

Abstract

The cholesterol molecule, like some other lipids, is very weakly soluble in water. It is present in all cells of humans, mainly in membranes and especially in specialized areas of the plasma membrane such as caveolae and rafts. These areas are rich in sphingomye-lin and carry out important functions like signaling. Cholesterol is also present in plasma and bile, but it is nearly absent from normal urine and spinal fluid. In plasma, cholesterol is localized in lipoprotein particles; in bile, it is in vesicles and micelles. The common denominators at these locations are phosphatidylcholine and sphingomyelin. Cholesterol is very mobile in this phospholipid environment; it flip-flops across the bilayer with a t1/2 of seconds, diffuses laterally with similar speed, and exchanges/transfers between membranes in proximity by aqueous diffusion or with the facilitation of soluble lipid transfer proteins. The reasons why lipoproteins, bile vesicles, and areas of the plasma membrane are cholesterol enriched are active areas of investigation.

Keywords

High Density Lipoprotein Cholesteryl Ester Free Cholesterol Mevalonic Acid Cholesterol Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Berge, K.E., Tian, H., Graf, G.A., Yu, L., Grishin, N.V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., and Hobbs, H.H., 2000, Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters, Science 290:1771–1775.CrossRefGoogle Scholar
  2. Berman, M., Beltz, W.F., Greif, P.C., Chabay, R., and Boston, R.C., 1983, CONSAM User’s Guide, Publication No. 1983–421–132:3279, U.S. Government Printing Office, Washington, DC.Google Scholar
  3. Berman, M., and Weiss, M.F., 1978, SAAM Manual, DHEW Publ. #78–180, U.S. Government Printing Office, Washington, DC.Google Scholar
  4. Brooks-Wilson, A., Marcil, M., Clee, S.M., Zhang, L.-H., Roomp, K., van Dam, M., Yu, L., Brewer, C, Collins, J.A., Molhuizen, H.O.F., Loubser, O., Ouelette, B.F.F., Fichter, K., Ashbourne-Excoffon, K.J.D., Sensen, C.W., Scherer, S., Mott, S., Denis, M., Martindale, D., Frohlich, J., Morgan, K., Koop, B., Pimstone, S., Kastelein, J.J.P., Genest, J. Jr., and Hayden, M.R., 1999, Mutations in ABC1 in Tangier disease and familial high density lipoprotein deficiency, Nature Genet. 22:336–;345.CrossRefGoogle Scholar
  5. Faix, D., Neese, R., Kletke, C, Wolden, S., Cesar, D., Coutlangus, M., Shackleton, C.H.L., and Hellerstein, M.K., 1993, Quantification of menstrual and diurnal periodicities in rates of cholesterol and fat synthesis in humans, J. Lipid Res 34:2063–2075.Google Scholar
  6. Foster, D.M., and Boston, R.C., 1983, The use of computers in compartmental analysis: The SAAM and CONSAM programs, in: Compartmental Distribution of Radiotracers, J.S. Robertson, ed., CRC Press Inc., Boca Raton.Google Scholar
  7. Francis, G.A., Knopp, R.H., and Oram, J.F., 1995, Defective removal of cellular cholesterol and phospholipids by apo A-l in Tangier disease, J. Clin. Invest. 96:78–87.CrossRefGoogle Scholar
  8. Grundy, S.M., 1982, Role of isotopes for determining absorption of cholesterol in man, in:Lipoprotein Kinetics and Modeling, M. Berman, S.M. Grundy, and B.V. Howard, eds., Academic Press, New York.Google Scholar
  9. Jones, P.J.H., Lichtenstein, A.H., and Schaefer, E.J., 1994, Interaction of dietary fat saturation and cholesterol level on cholesterol synthesis measured using deuterium incorporation, J. Lipid Res. 35:1093–1101.Google Scholar
  10. Korn, B.S., Shimomura, I., Bashmakov, Y., Hammer, R.E., Horton, J.D., Goldstein, J.L., and Brown, M.S., 1998, Blunted feedback suppression of SREBP processing by dietary cholesterol in transgenic mice expressing sterol-resistant SCAP (D443N), J. Clin. Invest. 102:2050–2060CrossRefGoogle Scholar
  11. Lee, W.N.P., Bassilian, S., Guo, Z., Schoeller, D., Edmond, J., Bergner, E.A., and Byerley, L.O., 1994, Measurement of fractional lipid synthesis using deuterated water (2H2O) and mass isotopomer analysis, Am. J. Physiol. 266:E372–E383.Google Scholar
  12. Liscum, L., and Underwood, K.W., 1995, Intracellular cholesterol transport and compartmentation, J. Biol. Chem. 270:15443–15446.CrossRefGoogle Scholar
  13. Quarfort, S.H., and Hilderman, H.L., 1970, Quantitation of the in vitro free cholesterol exchange between human red cells and lipoproteins, J. Lipid Res. 11:528–535.Google Scholar
  14. Schwartz, C, 1982, Cholesterol kinetics and modeling: introduction, in:Lipoprotein Kinetics and Modeling, M. Berman, S.M. Grundy, and B.V. Howard, eds., Academic Press, New York.Google Scholar
  15. Schwartz, C.C., Berman, M., Vlahcevic, Z.R., and Swell, L., 1982a, Multicompartmental analysis of cholesterol metabolism in man: quantitative kinetic evaluation of precursor sources and turnover of high density lipoprotein cholesterol esters, J Clin. Invest. 70:863–876.CrossRefGoogle Scholar
  16. Schwartz, C.C., Vlahcevic, Z.R., Berman, M., Meadows, J.G., Nisman, R.M., and Swell, L., 1982b, Central role of high density lipoprotein in plasma free cholesterol metabolism, J. Clin. Invest. 70:105–116.CrossRefGoogle Scholar
  17. Schwartz, C.C., Zech, L.A., VandenBroek, J.M., and Cooper, P.S., 1993, Cholesterol kinetics in subjects with bile fistula, J.Clin. Invest. 91:923–938.CrossRefGoogle Scholar
  18. Shamburek, R.D., Pentchev, P.G., Zech, L.A., Blanchette-Mackie, J., Carstea, E.D., VandenBroek, J.M., Cooper, P.S., Neufeld, E.B., Phair, R.D., Brewer, H.B., Brady, R.O., and Schwartz, C.C., 1997, Intracellular trafficking of the free cholesterol derived from LDL cholesteryl ester is defective in vivo in Niemann-Pick C disease: insights on normal metabolism of HDL and LDL gained from the NP-C mutation, J. Lipid Res. 38:2422–2435.Google Scholar
  19. Spady, D.K., and Dietschy J.M., 1983, Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat, J. Lipid Res. 24:303–315.Google Scholar
  20. Wong, W.W., Hachey, D.L., Feste, A., Leggitt, J., Clarke, L.L., Pond, W.G., and Klein, P.D., 1991, Measurement of in vivo cholesterol synthesis from 2H20: a rapid procedure for the isolation, combustion, and isotopic assay of erythrocyte cholesterol, J. Lipid Res. 32:1049–1056.Google Scholar
  21. Zech, L.A., 1982, Sensitivity in compartmental models, in:Lipoprotein Kinetics and Modeling, M. Berman, S.M. Grundy, and B.V. Howard, eds, Academic Press, New York.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Charles C. Schwartz
    • 1
    • 2
  • Julie M. VandenBroek
    • 1
  • Patricia S. Cooper
    • 1
  1. 1.Department of MedicineMedical College of Virginia, Virginia Commonwealth UniversityRichmond
  2. 2.Midlothian

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