Inhibition and Activation of Cholesteryl Ester Transfer and its Significance in Plasma Cholesterol Metabolism

  • Christopher J. Fielding
Part of the Advances in Experimetal Medicine and Biology book series (AEMB, volume 201)


Cholesteryl ester transfer in plasma can be defined as the catalyzed movement of preformed cholesteryl ester between lipoprotein particles. In mammalian plasma, this activity resides in one or more of a class of transfer proteins which show specificity for hydrophobic lipids such as cholesteryl and retinyl esters and triglycerides.1–3 It has been suggested that the mechanism of catalysis is in the ability of such transfer proteins to increase the solubility of these lipids in plasma and in that way increase diffusion rates between lipid surfaces.4 Alternatively, the transfer protein may facilitate complex formation between donor and acceptor lipoprotein particles.5 Studies using labeled cholesteryl esters and triglycerides indicate that transfer is bidirectional.6 However, the effective concentration of these lipids in different lipoproteins in usually not the same; as a result, the forward and back rates of transfer will not be identical and a net transfer of cholesteryl ester will result.


High Density Lipoprotein Cholesteryl Ester Transfer Protein Free Cholesterol Reverse Cholesterol Transport Cholesterol Acyltransferase 
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  1. 1.
    N. M. Pattnaik, A. Montes, L. B. Hughes, and D. B. Zilversmit, Choles-teryl ester exchange protein in human plasma. Isolation and characterization, Biochim. Biophys. Acta 530:428 (1978).PubMedCrossRefGoogle Scholar
  2. 2.
    J. Ihm, J. L. Ellsworth, B. Chataing, and J. A. K. Harmony, Plasma protein-facilitated coupled exchange of phosphatidylcholine and cholesteryl ester in the absence of cholesterol esterification, J. Biol. Chem. 257:4818 (1982).PubMedGoogle Scholar
  3. 3.
    J. J. H. Albers, J. J. Tollefson, C.-H. Chen, A. Steinmetz, Isolation and characterization of human plasma lipid transfer protein, Arteriosclerosis 4:49 (1984).PubMedCrossRefGoogle Scholar
  4. 4.
    L. R. McLean and M. C. Phillips, Mechanism of cholesterol and phosphatidylcholine exchange or transfer between unilamellar vesicles, Biochemistry 20:2893 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    J. I. Ihm, D. M. Quinn, S. J. Busch, B. Chataing, and J. A. K. Harmony, Kinetics of plasma protein-catalyzed exchange of phosphatidyl choline and cholesteryl ester between plasma lipoproteins, J. Lipid Res. 23:1328 (1982).PubMedGoogle Scholar
  6. 6.
    R. E. Morton and D. B. Zilversmit, Inter-relationship of lipids transferred by the lipid-transfer protein isolated from human lipoprotein-deficient plasma, J. Biol. Chem. 258:11751 (1983).PubMedGoogle Scholar
  7. 7.
    P. E. Fielding, C. J. Fielding, R. J. Havel, J. P. Kane, and P. Tun, Cholesterol net transport, esterification and transfer in human hyperlipidemic plasma, J. Clin. Invest 71:449 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    J. A. Glomset and K. R. Norum, The metabolic role of lecithin:cholesterol acyltransferase: perspectives from pathology, Adv. Lipid Res. 11:1 (1973).Google Scholar
  9. 9.
    P. E. Fielding and C. J. Fielding, A cholesteryl ester transfer complex in human plasma, Proc. Natl. Acad. Sci. USA 77:3327 (1980).PubMedCrossRefGoogle Scholar
  10. 10.
    M. C. Cheung and J. J. Albers, Characterization of lipoprotein particles isolated by immunoaffinity chromatography. Particles containing A-I and A-II and particles containing A-I but no A-II, J. Biol. Chem. 259:12201 (1984).PubMedGoogle Scholar
  11. 11.
    C. Chen, E. Applegate, W. C. King, J. A. Glomset, K. R. Norum, and E. Gjone, A study of the small spherical high density lipoproteins of patients afflicted with familial lecithin:cholesterol acyltransferase deficiency, J. Lipid Res. 25:269 (1984).PubMedGoogle Scholar
  12. 12.
    C. J. Fielding and P. E. Fielding, Purification and substrate specificity of lecithin:cholesterol acyltransferase from human plasma, FEBS Lett 15:355 (1971).PubMedCrossRefGoogle Scholar
  13. 13.
    P. J. Barter, Evidence that lecithin:cholesterol acyltransferase acts on both high density and low density lipoproteins, Biochim. Biophys. Acta 751:261 (1983).PubMedCrossRefGoogle Scholar
  14. 14.
    P. J. Barter and G. J. Hopkins, Relative rates of incorporation of esterified cholesterol into human very low and low density lipoproteins. In vitro studies of two separate pathways, Biochim. Biophys. Acta 751:33 (1983).PubMedCrossRefGoogle Scholar
  15. 15.
    T. Chajek and C. J. Fielding, Isolation and characterization of a human serum cholesteryl ester transfer protein, Proc. Natl. Acad. Sci. USA 75:3445 (1978).PubMedCrossRefGoogle Scholar
  16. 16.
    Y. L. Marcel, C. Vezina, B. Teng, and A. Sniderman, Transfer of cholesteryl esters between human high density lipoproteins and triglyc-eride-rich lipoproteins controlled by a plasma protein factor, Atherosclerosis 35:127 (1980).PubMedCrossRefGoogle Scholar
  17. 17.
    C. J. Fielding and P. E. Fielding, Regulation of human plasma lecithin: cholesterol acyltransferase activity by lipoprotein acceptor cholesteryl ester content, J. Biol. Chem. 256:2102 (1981).PubMedGoogle Scholar
  18. 18.
    R. J. Deckelbaum, S. Eisenberg, Y. Oschry, E. Butbul, I. Sharon, and T. Olivecrona, Reversible modification of human plasma low density lipoprotein towards triglyceride-rich precursors. A mechanism for losing excess cholesteryl esters. J. Biol. Chem. 257:6509 (1982).PubMedGoogle Scholar
  19. 19.
    C. J. Fielding, G. M. Reaven, G. Liu, and P. E. Fielding, Increased free cholesterol in plasma low and very low density lipoproteins in noninsulin-dependent diabetes mellitus: its role in the inhibition of cholesteryl ester transfer, Proc. Natl. Acad. Sci. USA 81:2512 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    G. R. Castro and C. J. Fielding, Effects of postprandial lipemia on plasma cholesterol metabolism, J. Clin. Invest, 75:874 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    A. Tall and D. Sammett, Mechanisms of enhanced cholesteryl ester (CE) transfer during alimentary lipemia, Circulation 72:111:287 (1985).Google Scholar
  22. 22.
    K. Bloch, Cholesterol: evolution of structure and function,, in “Biochemistry of Lipids and Membranes,” D. E. Vance and J. E. Vance, eds., Benjamin/Cummings, California (1985).Google Scholar
  23. 23.
    H. Dieplinger, P. Y. Schoenfeld, and C. J. Fielding, Plasma cholesterol transport in end stage renal disease, Circulation 72:111:199 (1985).Google Scholar
  24. 24.
    C. J. Fielding, The origin and properties of free cholesterol potential gradients in plasma, and their relation to atherogenesis, J. Lipid Res. 25:1624 (1984).PubMedGoogle Scholar
  25. 25.
    A. R. Tall, D. M. Small, D. Atkinson, and L. L. Rudel, Studies on the structure of low density lipoprotein isolated from Macaca Fascicu-laris fed an atherogenic diet, J. Clin. Invest. 62:1354 (1978).PubMedCrossRefGoogle Scholar
  26. 26.
    P. J. Barter, J. M. Gooden, and O. V. Rajaram, Species differences in the activity of a serum triglyceride transferring factor, Atherosclerosis 33:165 (1979).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Christopher J. Fielding
    • 1
  1. 1.Cardiovascular Research InstituteUniversity of CaliforniaSan FranciscoUSA

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